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Background: Proper catheter placement for convection-enhanced delivery (CED) is required to maximize tumor coverage and minimize exposure to healthy tissue. We developed an image-based model to patient-specifically optimize the catheter placement for rhenium-186 ( 186 Re)-nanoliposomes (RNL) delivery to treat recurrent glioblastoma (rGBM)., Methods: The model consists of the 1) fluid fields generated via catheter infusion, 2) dynamic transport of RNL, and 3) transforming RNL concentration to the SPECT signal. Patient-specific tissue geometries were assigned from pre-delivery MRIs. Model parameters were personalized with either 1) individual-based calibration with longitudinal SPECT images, or 2) population-based assignment via leave-one-out cross-validation. The concordance correlation coefficient (CCC) was used to quantify the agreement between the predicted and measured SPECT signals. The model was then used to simulate RNL distributions from a range of catheter placements, resulting in a ratio of the cumulative RNL dose outside versus inside the tumor, the "off-target ratio" (OTR). Optimal catheter placement) was identified by minimizing OTR., Results: Fifteen patients with rGBM from a Phase I/II clinical trial (NCT01906385) were recruited to the study. Our model, with either individual-calibrated or population-assigned parameters, achieved high accuracy (CCC > 0.80) for predicting RNL distributions up to 24 h after delivery. The optimal catheter placements identified using this model achieved a median (range) of 34.56 % (14.70 %-61.12 %) reduction on OTR at the 24 h post-delivery in comparison to the original placements., Conclusions: Our image-guided model achieved high accuracy for predicting patient-specific RNL distributions and indicates value for optimizing catheter placement for CED of radiolabeled liposomes., Competing Interests: Declaration of competing interest William T. Phillips discloses stock ownership and board membership in NanoTx, Inc., and is consultant for Plus Therapeutics, Inc. Andrew J. Brenner discloses financial Interests and stock ownership in NanoTx, Inc., and financial Interests and advisory role in Plus Therapeutics, Inc. Ryan T. Woodall owns stake in Cairina Inc. All other authors report no conflict of interest relevant to this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose of Review: Cardiac amyloidosis is a condition marked by the misfolding of precursor proteins into insoluble amyloid fibrils, leading to restrictive cardiomyopathy and heart failure symptoms. This review discusses advancements in nuclear imaging techniques that enhance the diagnosis and guide the management of cardiac amyloidosis, addressing the critical need for early and accurate detection in clinical practice., Recent Findings: Recent studies and guidelines emphasizes the pivotal role of nuclear imaging techniques in diagnosing cardiac amyloidosis. Cardiac scintigraphy, using bone-avid tracers like 99mTc-PYP, 99mTc-DPD, and 99mTc-HMDP, is instrumental in distinguishing between transthyretin amyloidosis and light chain amyloidosis. PET, with tracers such as 11C-Pittsburgh Compound B (11C-PiB) and 18F-Florbetapir, offers significant potential in measuring amyloid burden and monitoring disease progression, providing detailed insights into the myocardial involvement., Summary: The advancements in nuclear imaging techniques significantly impact the management of cardiac amyloidosis. These methods allow for a more accurate diagnosis, detailed assessment of disease extent, and better differentiation between amyloidosis types, which are crucial for tailoring treatment approaches. The integration of these techniques into clinical practice is essential for improving patient outcomes and advancing research in cardiac amyloidosis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Immunotherapy has dramatically altered the therapeutic landscape for oncology, but more research is needed to identify patients who are likely to achieve durable clinical benefit and those who may develop unacceptable side effects. We investigated the role of artificial intelligence in PET/SPECT-guided approaches for immunotherapy-treated patients., Methods: We performed a scoping review of MEDLINE, CENTRAL, and Embase databases using key terms related to immunotherapy, PET/SPECT imaging, and AI/radiomics through October 12, 2022., Results: Of the 217 studies identified in our literature search, 24 relevant articles were selected. The median (interquartile range) sample size of included patient cohorts was 63 (157). Primary tumors of interest were lung (n = 14/24, 58.3%), lymphoma (n = 4/24, 16.7%), or melanoma (n = 4/24, 16.7%). A total of 28 treatment regimens were employed, including anti-PD-(L)1 (n = 13/28, 46.4%) and anti-CTLA-4 (n = 4/28, 14.3%) monoclonal antibodies. Predictive models were built from imaging features using univariate radiomics (n = 7/24, 29.2%), radiomics (n = 12/24, 50.0%), or deep learning (n = 5/24, 20.8%) and were most often used to prognosticate (n = 6/24, 25.0%) or describe tumor phenotype (n = 5/24, 20.8%). Eighteen studies (75.0%) performed AI model validation., Conclusion: Preliminary results suggest broad potential for the application of AI-guided immunotherapy management after further validation of models on large, prospective, multicenter cohorts., Clinical Relevance Statement: This scoping review describes how artificial intelligence models are built to make predictions based on medical imaging and explores their application specifically in the PET and SPECT examination of immunotherapy-treated cancers., Key Points: • Immunotherapy has drastically altered the cancer treatment landscape but is known to precipitate response patterns that are not accurately accounted for by traditional imaging methods. • There is an unmet need for better tools to not only facilitate in-treatment evaluation but also to predict, a priori, which patients are likely to achieve a good response with a certain treatment as well as those who are likely to develop side effects. • Artificial intelligence applied to PET/SPECT imaging of immunotherapy-treated patients is mainly used to make predictions about prognosis or tumor phenotype and is built from baseline, pre-treatment images. Further testing is required before a true transition to clinical application can be realized., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: [ 123 I]I-FP-CIT SPECT is an imaging tool to support the diagnosis of parkinsonian syndromes characterized by nigrostriatal dopaminergic degeneration. After intravenous injection, [ 123 I]I-FP-CIT is metabolized for a small part by the enzyme CYP3A4, leading to the formation of [ 123 I]I-nor-β-CIT. [ 123 I]I-nor-β-CIT passes the blood-brain barrier and has a very high affinity for the serotonin transporter (SERT). The SERT is expressed in the striatum and cortical areas. So, at least theoretical, the use of frequently used CYP3A4 inhibitors (like amiodarone) may influence the specific to non-specific striatal [ 123 I]I-FP-CIT ratio. Here we tested this novel hypothesis., Methods: Using a retrospective design, we determined the specific to non-specific striatal [ 123 I]I-FP-CIT ratio (using BRASS software) in 6 subjects that were using an CYP3A4 inhibitor and 18 matched controls. Only subjects were included with a normal rated [ 123 I]I-FP-CIT SPECT scan, and all participants were scanned on the same brain-dedicated SPECT system., Results: The specific to non-specific (assessed in the occipital cortex) striatal [ 123 I]I-FP-CIT binding ratio was significantly higher in CYP3A4 users than in the control group (3.52 ± 0.33 vs. 2.90 ± 0.78, p < 0.001)., Conclusion: Our preliminary data suggest that the use of CYP3A4 inhibitors may influence striatal [ 123 I]I-FP-CIT binding ratios. This information, when reproduced in larger studies, may be relevant for studies in which quantification of [ 123 I]I-FP-CIT SPECT imaging is used for diagnostic or research purposes., (© 2024. The Author(s).)

Competing Interests: Conflict of interest: None declared.

Objective: This study aimed to retrospectively assess the benefits of combining low-dose computed tomography (LDCT) with ventilation/perfusion single-photon emission computed tomography (V/Q SPECT) for the diagnosis of pulmonary embolism (PE)., Methods: A retrospective analysis was performed on 92 patients with suspected PE who underwent V/Q SPECT with ldCT (V/Q SPECT CT) between January 2020 and December 2022 at King Khalid Hospital Najran. Data were collected using the hospital's picture archiving and communication system. Scans were categorized on the basis of perfusion defects, matched or mismatched ventilation, and CT findings. The specificity of V/Q SPECT CT was compared with that of Q SPECT CT., Results: This study included 92 patients (54 females and 38 males; median age, 53 years). The results demonstrated that V/Q SPECT CT had higher specificity (93%) than V/Q SPECT alone (88%). If CT had been used as a ventilation substitute, 21% of patients would have been reported to be positive for PE (8% false-positive), yielding a specificity of 60% for Q SPECT CT. These findings align with the existing literature, although discrepancies in specificity values were noted due to the different study designs and sample sizes., Conclusion: This study highlights the enhanced specificity of V/Q SPECT CT compared to V/Q SPECT and Q SPECT CT alone. Including low-dose CT improves diagnostic accuracy by reducing false positives and providing detailed anatomical information. V/Q SPECT CT offers superior specificity in diagnosing PE compared with V/Q SPECT alone, supporting its use in clinical practice.

The etiology of brain fog associated with long COVID is not clear. Based on some preliminary work, disruption of the blood-brain barrier has been hypothesized, but has not been tested in patients with long COVID. In this case-control pilot study, we evaluated blood-brain barrier permeability in patients with long COVID and subjective memory loss or brain fog. We used 99 m Technetium diethylenetriaminepentaacetic acid single-photon emission computed tomography (SPECT) to measure blood-brain barrier permeability and a telephone assessment (T-cog) to measure cognitive function. The blood-brain barrier permeability was quantified via SPECT standard uptake value (SUV). We assessed the blood-brain barrier permeability in 14 long COVID patients and 10 control participants without subjective cognitive impairment or brain fog. Participants in the two groups were similar in age. The long COVID group had more comorbidities compared to the control group. There was no difference in the SUVs in the long COVID (0.22 ± 0.12) vs the control (0.17 ± 0.04) group. There was no difference in the T-cog results in the two groups either. We found no evidence of a difference in blood-brain permeability in patients with long COVID when compared to controls without a known history of COVID-19 infection. Larger studies are needed to confirm these findings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Poststroke neuroinflammation exacerbates disease progression. [ 11 C]PK11195-positron emission tomography (PET) imaging has been used to visualize neuroinflammation; however, its short half-life of 20 min limits its clinical use. [ 123 I]CLINDE has a longer half-life (13h); therefore, [ 123 I]CLINDE-single-photon emission computed tomography (SPECT) imaging is potentially more practical than [ 11 C]PK11195-PET imaging in clinical settings. The objectives of this study were to 1) validate neuroinflammation imaging using [ 123 I]CLINDE and 2) investigate the mechanisms underlying stroke in association with neuroinflammation using multimodal techniques, including magnetic resonance imaging (MRI), gas-PET, and histological analysis, in a rat model of ischemic stroke, that is, permanent middle cerebral artery occlusion (pMCAo). At 6 days post-pMCAo, [ 123 I]CLINDE-SPECT considerably corresponded to the immunohistochemical images stained with the CD68 antibody (a marker for microglia/microphages), comparable to the level observed in [ 11 C]PK11195-PET images. In addition, the [ 123 I]CLINDE-SPECT images corresponded well with autoradiography images. Rats with severe infarcts, as defined by MRI, exhibited marked neuroinflammation in the peri-infarct area and less neuroinflammation in the ischemic core, accompanied by a substantial reduction in the cerebral metabolic rate of oxygen (CMRO 2 ) in 15 O-gas-PET. Rats with moderate-to-mild infarcts exhibited neuroinflammation in the ischemic core, where CMRO 2 levels were mildly reduced. This study demonstrates that [ 123 I]CLINDE-SPECT imaging is suitable for neuroinflammation imaging and that the distribution of neuroinflammation varies depending on the severity of infarction., Competing Interests: Declaration of competing interest, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Left bundle branch block (LBBB) represents a frequently encountered conduction system disorder. Despite its widespread occurrence, a continual dilemma persists regarding its intricate association with underlying cardiomyopathy and its pivotal role in the initiation of dilated cardiomyopathy. The pathologic alterations linked to LBBB-induced cardiomyopathy (LBBB-CM) have remained elusive., Objective: This study sought to investigate the chronologic dynamics of LBBB to left ventricular dysfunction and the pathologic mechanism of LBBB-CM., Methods: LBBB model was established through main left bundle branch trunk ablation in 14 canines. All LBBB dogs underwent transesophageal echocardiography and electrocardiography before ablation and at 1 month, 3 months, 6 months, and 12 months after LBBB induction. Single-photon emission computed tomography imaging was performed at 12 months. We then harvested the heart from all LBBB dogs and 14 healthy adult dogs as normal controls for anatomic observation, Purkinje fiber staining, histologic staining, and connexin43 protein expression quantitation., Results: LBBB induction caused significant fibrotic changes in the endocardium and mid-myocardium. Purkinje fibers exhibited fatty degeneration, vacuolization, and fibrosis along with downregulated connexin43 protein expression. During a 12-month follow-up, left ventricular dysfunction progressively worsened, peaking at the end of the observation period. The association between myocardial dysfunction, hypoperfusion, and fibrosis was observed in the LBBB-afflicted canines., Conclusion: LBBB may lead to profound myocardial injury beyond its conduction impairment effects. The temporal progression of left ventricular dysfunction and the pathologic alterations observed shed light on the complex relationship between LBBB and cardiomyopathy. These findings offer insights into potential mechanisms and clinical implications of LBBB-CM., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. All rights reserved.)

We present a new method to measure sub-microcurie activities of photon-emitting radionuclides in organs and lesions of small animals in vivo. Our technique, named the collimator-less likelihood fit, combines a very high sensitivity collimatorless detector with a Monte Carlo-based likelihood fit in order to estimate the activities in previously segmented regions of interest along with their uncertainties. This is done directly from the photon projections in our collimatorless detector and from the region of interest segmentation provided by an x-ray computed tomography scan. We have extensively validated our approach with 225Ac experimentally in spherical phantoms and mouse phantoms, and also numerically with simulations of a realistic mouse anatomy. Our method yields statistically unbiased results with uncertainties smaller than 20% for activities as low as ~111Bq (3nCi) and for exposures under 30 minutes. We demonstrate that our method yields more robust recovery coefficients when compared to SPECT imaging with a commercial pre-clinical scanner, specially at very low activities. Thus, our technique is complementary to traditional SPECT/CT imaging since it provides a more accurate and precise organ and tumor dosimetry, with a more limited spatial information. Finally, our technique is specially significant in extremely low-activity scenarios when SPECT/CT imaging is simply not viable.

Monoclonal antibodies and antibody fragments have proven to be highly effective vectors for the delivery of radionuclides to target tissues for positron emission tomography (PET) and single-photon emission computed tomography (SPECT). However, the stochastic methods that have traditionally been used to attach radioisotopes to these biomolecules inevitably produce poorly defined and heterogeneous probes and can impair the ability of the immunoglobulins to bind their molecular targets. In response to this challenge, an array of innovative site-specific and site-selective bioconjugation strategies have been developed, and these approaches have repeatedly been shown to yield better-defined and more homogeneous radioimmunoconjugates with superior in vivo performance than their randomly modified progenitors. In this Current Opinion in Chemical Biology review, we will examine recent advances in this field, including the development - and, in some cases, clinical translation - of nuclear imaging agents radiolabeled using strategies that target the heavy chain glycans, peptide tags, and unnatural amino acids., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brian Zeglis has patent #US11000604B2 issued to None. Brian Zeglis has patent #CA3230848A1 pending to Zentera Therapeutics. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Three-dimensional (3D) ventilation flow capacity-weighted (VFCW) maps together with 3D ventilation-weighted (VW) maps may help to better assess pulmonary function., Purpose: To investigate the use of 3D VFCW and VW maps for evaluating pulmonary ventilation function., Study Type: Prospective., Population: Two patients (one male, 85 years old; one female, 64 years old) with chronic obstructive pulmonary disease (COPD) and nine healthy subjects (all male; 23-27 years)., Field Strength/sequence: 3-T, 3D radial UTE imaging., Assessment: 3D VFCW and VW maps were calculated from 3D UTE MRI by voxel-wise subtraction of respiratory phase images. Their validation was tested in nine healthy volunteers using slow/deep and fast/shallow breathing conditions. Additional validation was performed by comparison with single photon emission computed tomography (SPECT) ventilation maps of one healthy participant. For comparison, gravity dependence of anterior-posterior regional ventilation was assessed by one-dimensional plot of the mean signal intensity for each coronal slice. Structural similarity index measure was also calculated. Finally, VW maps and VFCW maps of two COPD patients were evaluated for emphysema lesions with reference to CT images., Statistical Tests: Wilcoxon sign-rank tests for regional Ventilation and ventilation flow capacity, analysis of variance, post-hoc t-tests and Bonferroni correction, coefficient of variation, Kullback-Liebler divergence. A P-value <0.05 was considered statistically significant., Results: The validation of 3D VFCW and VW maps was shown by statistically significant differences in ventilation flow capacity and ventilation between the breathing conditions. Additionally, UTE-MRI and SPECT-based ventilation maps showed gravitational dependence in the anteroposterior direction. When applied to patients with COPD, the use of 3D VFCW and VW maps was able to differentiate between two patients with different phenotypes., Data Conclusion: The use of 3D VFCW and VW maps can provide regional information on ventilation function and potentially contribute to assessment of COPD subtypes and disease progression., Evidence Level: 2 TECHNICAL EFFICACY: Stage 1., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background: Advances in molecular imaging strategies have had an effect on precise diagnosis and treatment. Research has been intensified to develop more effective and versatile radiopharmaceuticals to uplift diagnostic efficiency and, consequently, the treatment., Purpose: To label the flutamide (FLUT) coupled with diethylenetriamine pentaacetate (DTPA) with technetium-99 m ( 99m Tc) and to evaluate its binding efficiency with rhabdomyosarcoma (RMS) cancer cells., Material and Methods: Radiolabeling of FLUT with 185 MBq freshly eluted 99m TcO 4 -1 was carried out via DTPA bifunctional chelating agent using stannous chloride reducing agent at pH 5. The labeled compound was assessed for its purity using chromatography analysis, stability in saline and blood serum, AND charge using paper electrophoresis. Normal biodistribution was studied using a mouse model, while binding affinity with RMS cancer cells was studied using an internalization assay. The in vivo accumulation of RMS cancer cells in a rabbit model was monitored using a SPECT gamma camera., Results: Radiolabeling reaction displayed a pharmaceutical yield of 97% and a stability assay showed >95% intact radiopharmaceutical up to 6 h in saline and blood serum. In vitro internalization studies showed the potential of [ 99m Tc]DTPA-FLUT to enter into cancer cells. This biodistribution study showed rapid blood clearance and minimum uptake by body organs, and scintigraphy displayed the [ 99m Tc]DTPA-FLUT uptake by lesion, induced by RMS cancer cell lines in rabbit., Conclusion: Stable, newly developed [ 99m Tc]DTPA-FLUT seeks its way to internalize into RMS cancer cells, indicating it could be a potential candidate for the diagnosis of RMS cancer., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Despite being time-consuming, SPECT/CT data is necessary for accurate dosimetry in patient-specific radiopharmaceutical therapy. We investigated how reducing the frame duration (FD) during SPECT acquisition can simplify the dosimetry workflow for [ 177 Lu]Lu-PSMA radioligand therapy (RLT). We aimed to determine the impact of shortened acquisition times on dosimetric precision. Three SPECT scans with FD of 20, 10, and 5 second/frame (sec/fr) were obtained 48 h post-RLT from one metastatic castration-resistant prostate cancer (mCRPC) patient's pelvis. Planar images at 4, 48, and 72 h post-therapy were used to calculate time-integrated activities (TIAs). Using accurate activity calibrations and GATE Monte Carlo (MC) dosimetry, absorbed doses in tumor lesions and kidneys were estimated. Dosimetry precision was assessed by comparing shorter FD results to the 20 sec/fr reference using relative percentage difference (RPD). We observed consistent calibration factors (CFs) across different FDs. Using the same CF, we obtained marginal RPD deviations less than 4% for the right kidney and tumor lesions and less than 7% for the left kidney. By reducing FD, simulation time was slightly decreased. This study shows we can shorten SPECT acquisition time in RLT dosimetry by reducing FD without sacrificing dosimetry accuracy. These findings pave the way for streamlined personalized internal dosimetry workflows., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: To evaluate the efficacy and safety of the advanced technique for positioning the endocardial electrodes of a cardiac contractility modulation (CCM) device., Materials and Methods: The CCM system was implanted in 100 patients, of which 60 CCM electrodes were positioned in the most optimal zones of myocardial perfusion, in particular, in the zone of the minor focal-scar/fibrotic lesion (the Summed Rest Score of 0 to 1-2, the intensity of the radiopharmaceutical at least 30%), and in 40 patients according to the standard procedure. Before the implantation of the CCM system, 60 patients underwent tomography (S-SPECT) of the myocardium with 99m Tc-methoxy-isobutyl-isonitrile at rest to determine the most optimal electrode positioning zones and 100 patients underwent transthoracic echocardiography at baseline and after 12 months to assess the effectiveness of surgical treatment., Results: Improved ventricular electrode positioning technique is associated with the best reverse remodeling of the left ventricular myocardium, especially in patients with ischemic chronic heart failure, with less radiation exposure to the surgeon and the patient, and without electrode-related complications., Conclusion: At the preoperative stage, it is recommended to perform a synchronized single-photon emission computed tomography of the myocardium with 99m Tc-methoxy-isobutyl-isonitrile at rest before implantation of the CCM device to assess the presence of scar zones/myocardial fibrosis in the anterior and inferior septal regions of the interventricular septum of the left ventricle, followed by implantation of ventricular electrodes in the zone of the minor scar/fibrous lesion, which will allow to achieve optimal stimulation parameters, increase the effectiveness of CCM therapy, reduce the radiation exposure on medical personnel and the patient during surgery.

Background: It has been reported that patients with geriatric psychiatric disorders include many cases of the prodromal stages of neurodegenerative diseases. Abnormal 123 I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane dopamine transporter single-photon emission computed tomography (DAT-SPECT) reveals a nigrostriatal dopaminergic deficit and is considered useful to detect dementia with Lewy bodies and Parkinson's disease as well as progressive supranuclear palsy and corticobasal degeneration. We aimed to determine the proportion of cases that are abnormal on DAT-SPECT in patients with geriatric psychiatric disorders and to identify their clinical profile., Methods: The design is a cross-sectional study. Clinical findings of 61 inpatients aged 60 years or older who underwent DAT-SPECT and had been diagnosed with psychiatric disorders, but not neurodegenerative disease or dementia were analysed., Results: 36 of 61 (59%) had abnormal results on DAT-SPECT. 54 of 61 patients who had DAT-SPECT (89%) had undergone 123 I-metaiodobenzylguanidine myocardial scintigraphy ( 123 I-MIBG scintigraphy); 12 of the 54 patients (22.2%) had abnormal findings on 123 I-MIBG scintigraphy. There were no cases that were normal on DAT-SPECT and abnormal on 123 I-MIBG scintigraphy. DAT-SPECT abnormalities were more frequent in patients with late-onset (55 years and older) psychiatric disorders (69.0%) and depressive disorder (75.7%), especially late-onset depressive disorder (79.3%)., Conclusion: Patients with geriatric psychiatric disorders include many cases showing abnormalities on DAT-SPECT. It is suggested that these cases are at high risk of developing neurodegenerative diseases characterised by a dopaminergic deficit. It is possible that patients with geriatric psychiatric disorders with abnormal findings on DAT-SPECT tend to show abnormalities on DAT-SPECT first rather than on 123 I-MIBG scintigraphy., Competing Interests: Competing interests: STa has received honoraria for his participation as a speaker at educational events sponsored by Sumitomo Pharma and Viatris. MF has received honoraria for his participation as a speaker at educational events sponsored by Eisai and Mochida Pharma. MT has received honoraria for his participation as a speaker at educational events sponsored by Otsuka Pharma, Sumitomo Pharma, Tsumura, Lundbeck Japan, Eisai, Meiji Seika Pharma, Viatris, Mitsubishi Tanabe Pharma, Janssen Pharma and Takeda Pharma. MT has received unrestricted research funding from Otsuka Pharma, Sumitomo Pharma, Eisai and Mochida Pharma (paid to the institution)., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

To investigate the feasibility of detection of apoptosis in vivo by 99mTc-HYNIC-Annexin V, Annexin V was labeled with 99mTc through HYNIC. 18 New Zealand rabbits implanted VX-2 were randomly divided into control (n = 8) and paclitaxel (PAC, n = 10) groups, given 2 mL/kg of normal saline or 2.4 mg/kg of PAC intravenously. The liver tumor imaging was detected by SPECT through intravenous injection of 99mTc-HYNIC-Annexin V before treatment, 24 hours and 48 hours after treatment respectively. Tumor radioactive count proportion to non-tumor sites was calculated. When the last imaging was finished, the rabbits were sacrificed. The tumor was taken out and divided into two pieces, one for TUNEL immunohistochemical analysis and the other for flow cytometry (FCM). We found that the rate of Annexin V labeled with 99mTc through HYNIC was more than 95%, and radiochemical purity was above 95%. The SPECT showed that two groups had no significant tumor imaging before the treatment. There is no significant tumor imaging in control group, while the PAC group 24 h and 48 h after treatment showed significant accumulation. The Tumor/non-Tumor (T/NT) in PAC group at 24 h and 48 h after chemotherapy was significantly different from that in the control group and PAC group prior to treatment. There was no significant difference between 24 h and 48 h in PAC group. The TUNEL-positive cells detected by immunohistochemistry and apoptotic rate detected by FCM in PAC group were significant different from those in control group. The T/NT was significantly correlated to TUNEL-positive cells and apoptotic rate of the tumor. PAC can induce apoptosis of rabbit VX-2 liver cancer cells. 24-48 h after paclitaxel chemotherapy is a window time for apoptosis detection. Apoptotic cells in vivo can be detected by SPECT through 99mTc-HYNIC-Annexin V.

Dynamic assessment of myocardial blood flow (MBF) and myocardial flow reserve (MFR) provides additional information that can improve diagnostic accuracy of radionuclide myocardial perfusion imaging in some clinical situations. This study assessed processing repeatability of these parameters calculated using two models-net retention (RET) and one compartment (1CM) in dynamic SPECT studies, using the latest version of Corridor 4DM software (v2024). Data of 107 patients were analyzed retrospectively (57 of whom were assessed in our previous study using 4DM v2015). Dynamic SPECT studies were carried out using a routine two-day rest-dipyridamole protocol. Data was processed in 4DM v2024 twice by one operator and once by another operator. Automatic heart image positioning during post-processing in 4DM v2024 was significantly improved compared to v2015, reducing the number of studies requiring extensive manual corrections from 41 to 12%. This significantly improved interobserver processing repeatability of MFR values in RCA territory compared to our previous study using v2015-from r = 0.67 to 0.85 (p = 0.0034). Interobserver processing repeatability of MBF and MFR in all 107 patients was significantly better in RET model compared to 1CM model. In conclusion, RET model is more reliable for calculating MBF and MFR values based on dynamic SPECT studies., (© 2024. The Author(s).)

Objective: Parkinson's disease (PD) is an age-related neurodegenerative condition characterized mostly by motor symptoms. Although a wide range of non-motor symptoms (NMS) are frequently experienced by PD patients. One of the important and common NMS is cognitive impairment, which is measured using different cognitive scales. Monitoring cognitive impairment and its decline in PD is essential for patient care and management. In this study, our goal is to identify the most effective cognitive scale in predicting cognitive decline over a 5-year timeframe initializing clinical biomarkers and DAT SPECT., Methods: Machine Learning has previously shown superior performance in image and clinical data classification and detection. In this study, we propose to use machine learning with different types of data, such as DAT SPECT and clinical biomarkers, to predict PD-CD based on various cognitive scales. We collected 330 DAT SPECT images and their clinical data in baseline, years 2,3,4, and 5 from Parkinson's Progression Markers Initiative (PPMI). We then designed a 3D Autoencoder to extract deep radiomic features (DF) from DAT SPECT images, and we then concatenated it with 17 clinical features (CF) to predict cognitive decline based on Montreal Cognitive Assessment (MoCA) and The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-I)., Results: The utilization of MoCA as a cognitive decline scale yielded better performance in various years compared to MDS-UPDRS-I. In year 4, the application of the deep radiomic feature resulted in the highest achievement, with a cross-validation AUC of 89.28, utilizing the gradient boosting classifier. For the MDS-UPDRS-I scale, the highest achievement was obtained by utilizing the deep radiomic feature, resulting in a cross-validation AUC of 81.34 with the random forest classifier., Conclusions: The study findings indicate that the MoCA scale may be a more effective predictor of cognitive decline within 5 years compared to MDS-UPDRS-I. Furthermore, deep radiomic features had better performance compared to sole clinical biomarkers or clinical and deep radiomic combined. These results suggest that using the MoCA score and deep radiomic features extracted from DAT SPECT could be a promising approach for identifying individuals at risk for cognitive decline in four years. Future research is needed to validate these findings and explore their utility in clinical practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gorji, Jouzdani. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Peripheral artery disease (PAD) is classified as the narrowing or complete occlusion of the lower extremity arteries due to atherosclerosis. The risk of developing PAD increases with increased age and risk factors such as smoking, diabetes, hypertension, and hypercholesterolemia. Current treatment for PAD involves lifestyle and symptom management, statin and antiplatelet therapy, and/or surgical interventions to improve quality of life with varying efficacy. PAD affects approximately 5 to 6 percent of the global population, with this global burden continuing to increase. Despite the increase in disease prevalence, no gold standard functional diagnostic tool has been established for enabling early detection of the disease, appropriate medical management, and prediction of adverse outcomes for PAD patients. The visualization and quantification of the physiological consequences of PAD are possible by way of nuclear imaging: specifically, via scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) imaging. These non-invasive modalities, when combined with targeted radionuclides, possess utility for detecting functional perfusion deficits and provide unique insight into muscle tissue- and vascular-level characteristics of PAD patients. This review discusses the past, present, and emerging applications of hybrid nuclear imaging modalities in the evaluation and monitoring of patients with PAD.

Background: Parkinson's disease (PD), and other parkinsonian syndromes are known to cause striatonigral dopaminergic system dysfunction and autonomic disturbances, including the vasomotor and sudomotor nervous systems. The detection of 123 I-FP-CIT SPECT (DaT scan) imaging and autonomic dysfunction helps differentiate PD from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). The sympathetic skin response (SSR) is a simple, non-invasive electrophysiological test that assesses the sympathetic sudomotor nervous system. It is reported that the SSR is impaired in patients with PD, MSA, and PSP., Objective: To study the relationship between SSR, 123 I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy and DaT scan imaging parameters in patients with PD, MSA, and PSP., Methods: The study included 62, 25, and 19 patients with PD, MSA, and PSP, respectively. The SSR, MIBG cardiac scintigraphy, and DaT scan imaging were examined. The amplitude and latency of the SSR were measured in all limbs and were compared with the results of MIBG cardiac scintigraphy and DAT scan imaging., Results: The SSR amplitudes were lower than reported normal subjects' reference values in PD, MSA, and PSP. The SSR amplitude only correlated with MIBG cardiac scintigraphy and DaT scan imaging parameters in PD. Multiple regression analyses also showed a significant relationship between the amplitudes of SSR and DaT scan imaging in PD., Conclusion: Unlike MSA, and PSP, the sudomotor nervous system is parallelly involved with cardiac sympathetic and central dopaminergic dysfunction from the early stage of PD., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest relevant to this work., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Cerebral hyperperfusion (CHP) occurred frequently after direct superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery for moyamoya disease (MMD). We analyzed cortical microvascular density (CMD) and the change of cerebral blood flow (LΔCBF) using intraoperative laser speckle contrast imaging (LSCI) on 130 hemispheres of 95 consecutive adult patients with MMD. The demographic characteristics, cortical hemodynamic sources, bypass methods, intraoperative blood flow data, and relative CBF changes on single-photon emission computed tomography (SPECT) examination (SΔrCBF) were compared between the groups with and without CHP. The median values for CMD, LΔCBF, and SΔrCBF were significantly higher in the CHP group than in the non-CHP group (CMD 0.240 vs 0.206, P  = 0.004; LΔCBF 2.285 vs 1.870, P <  0.001; SΔCBF 1.535 vs 1.260, P <  0.001). Multivariate analysis revealed that hemodynamic sources of recipient parasylvian cortical arteries from MCA (M-PSCAs), end-to-side (E-S) bypass method, CMD ≥ 0.217, and LΔCBF ≥ 1.985 were the risk factors for CHP. Intraoperative LSCI was useful for evaluating hemodynamics and predicting CHP in patients with MMD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Poly ADP-ribose polymerase (PARP) plays an important role in the DNA repair process and has become an attractive target for cancer therapy in recent years. Given that niraparib has good clinical efficacy as a PARP inhibitor, this study aimed to develop radiolabeled niraparib derivatives for tumor imaging to detect PARP expression and improve the accuracy of stratified patient therapy. The niraparib isonitrile derivative (CNPN) was designed, synthesized, and radiolabeled to obtain the [ 99m Tc]Tc-CNPN complex with high radiochemical purity (>95%). It was lipophilic and stable in vitro . In HeLa cell experiments, the uptake of [ 99m Tc]Tc-CNPN was effectively inhibited by the ligand CNPN, indicating the binding affinity for PARP. According to the biodistribution studies of HeLa tumor-bearing mice, [ 99m Tc]Tc-CNPN has moderate tumor uptake and can be effectively inhibited, demonstrating its specificity for targeting PARP. The SPECT imaging results showed that [ 99m Tc]Tc-CNPN had tumor uptake at 2 h postinjection. All of the results of this study indicated that [ 99m Tc]Tc-CNPN is a promising tumor imaging agent that targets PARP.

Background: Phenotypes of CANVAS are increasingly diversified, including bradykinesia and dysautonomia, so that its primary differential diagnoses are multiple system atrophy-cerebellar type (MSA-c), and spinocerebellar ataxia type 3 (SCA3). This case series aims to highlight key molecular imaging findings in CANVAS., Cases: We report a case series of six patients with CANVAS who underwent nuclear medicine examinations in our center and 13 patients from the literature. These include 18 F-FDG brain positron emission tomography (PET), single photon emission computed tomography (SPECT) of dopamine transporter (DaT) activity, and 123 I-MIBG cardiac scintigraphy of noradrenergic transmission., Conclusions: In CANVAS, 18 F-FDG brain PET mainly shows cerebellar hypometabolism, with preserved brainstem and striatum metabolism, contrasting with SCA3 and MSA-c. Dopaminergic denervation on scintigraphy seems to be associated with clinical parkinsonism, ranging from normal to severely impaired DaT SPECT. Additionally, 123 I-MIBG cardiac scintigraphy might show denervation in CANVAS, similar to SCA3, but not in most MSA-c patients., (© 2024 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

The tumor uptake of large non-targeted nanocarriers primarily occurs through passive extravasation, known as the enhanced permeability and retention (EPR) effect. Prior studies demonstrated improved tumor uptake and retention of 4-arm 40 kDa star polyethylene glycol (StarPEG) polymers for cancer imaging by adding prostate-specific membrane antigen (PSMA) targeting small molecule ligands. To test PSMA-targeted delivery and therapeutic efficacy, StarPEG nanodrugs with/without three copies of PSMA-targeting ligands, ACUPA, are designed and synthesized. For single-photon emission computed tomography (SPECT) imaging and therapy, each nanocarrier is labeled with 177Lu using DOTA radiometal chelator. The radiolabeled nanodrugs, [177Lu]PEG-(DOTA)1 and [177Lu]PEG-(DOTA)1(ACUPA)3, are evaluated in vitro and in vivo using PSMA+ PC3-Pip and/or PSMA- PC3-Flu cell lines, subcutaneous xenografts and disseminated metastatic models. The nanocarriers are efficiently radiolabeled with 177Lu with molar activities 10.8-15.8 MBq/nmol. Besides excellent in vitro PSMA binding affinity (kD = 51.7 nM), the targeted nanocarrier, [177Lu]PEG-(DOTA)1(ACUPA)3, demonstrated excellent in vivo SPECT imaging contrast with 21.3% ID/g PC3-Pip tumors uptake at 192 h. Single doses of 18.5 MBq [177Lu]PEG-(DOTA)1(ACUPA)3 showed complete resolution of the PC3-Pip xenografts observed up to 138 days. Along with PSMA-targeted excellent imaging contrast, these results demonstrated high treatment efficacy of [177Lu]PEG-(DOTA)1(ACUPA)3 for prostate cancer, with potential for clinical translation., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background: Brain magnetic resonance imaging voxel-based morphometry (VBM) and perfusion single-photon emission computed tomography (SPECT) are useful for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD)., Purpose: To determine whether combining multiple parameters of VBM and SPECT using a multiparametric scoring system (MSS) improves diagnostic accuracy in differentiating DLB from AD., Material and Methods: In total, 23 patients with DLB and 57 patients with AD underwent imaging using a voxel-based specific regional analysis system for AD (VSRAD), an easy Z-score imaging system, and a Z-Graph using three-dimensional stereotactic surface projection. The cutoff values were determined using the receiver operating characteristic curve to differentiate DLB from AD for all parameters. Patients were scored 1 (DLB) or 0 (AD) for each statistically significant parameter, according to a threshold. The total score was determined for each case to obtain a cutoff value for the MSS., Results: The mean Z-scores in the medial temporal lobes using the VSRAD were significantly lower in patients with DLB than in those with AD. Each Z-score of the summed Z-scores in all four segmented regions of the occipital lobes using the Z-Graph was significantly higher in patients with DLB than in those with AD. Among the five parameters, the highest accuracy was 80% for the Z-score of the summed Z-scores in the left medial occipital lobe. For the MSS, a cutoff value of four improved the diagnostic accuracy to 82%., Conclusion: MSS was more accurate than any single parameter of VBM or SPECT in differentiating DLB from AD., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: We sought to develop a novel deep learning (DL) workflow to interpret single-photon emission computed tomography (SPECT) wall motion., Background: Wall motion assessment with SPECT is limited by image temporal and spatial resolution. Visual interpretation of wall motion can be subjective and prone to error. Artificial intelligence (AI) may improve accuracy of wall motion assessment., Methods: A total of 1038 patients undergoing rest electrocardiogram (ECG)-gated SPECT and echocardiography were included. Using echocardiography as truth, a DL-model (DL-model 1) was trained to predict the probability of abnormal wall motion. Of the 1038 patients, 317 were used to train a DL-model (DL-model 2) to assess regional wall motion. A 10-fold cross-validation was adopted. Diagnostic performance of DL was compared with human readers and quantitative parameters., Results: The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) of DL model (AUC: .82 [95% CI: .79-.85]; ACC: .88) were higher than human (AUC: .77 [95% CI: .73-.81]; ACC: .82; P < .001) and quantitative parameter (AUC: .74 [95% CI: .66-.81]; ACC: .78; P < .05). The net reclassification index (NRI) was 7.7%. The AUC and accuracy of DL model for per-segment and per-vessel territory diagnosis were also higher than human reader. The DL model generated results within 30 seconds with operable guided user interface (GUI) and therefore could provide preliminary interpretation., Conclusions: DL can be used to improve interpretation of rest SPECT wall motion as compared with current human readers and quantitative parameter diagnosis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Reduced pulmonary diffusing capacity for carbon monoxide (D LCO ) can be observed in pulmonary arterial hypertension (PAH) and associates with increased mortality. However, the prognostic value of D LCO when corrected for haemoglobin (D LCOc ), an independent modifier of D LCO , remains understudied. Additionally, the prognostic role of ventilation (V)-perfusion (Q) emission computed tomography (V/Q SPECT) findings in patients with PAH, which may concurrently be performed to rule out chronic thromboembolic pulmonary hypertension, is uncertain. A retrospective cohort study was conducted on 152 patients with PAH referred to a tertiary hospital for evaluation from January 2011 to January 2020. Lung function tests, clinical data and V/Q SPECT were ascertained. Cox regression analysis was performed to evaluate the association between D LCOc , D LCO and V/Q SPECT defects at referral with all-cause mortality. In equally adjusted Cox regression analysis, each percentage increase in D LCOc % predicted (%pred) (hazard ratio (HR) 0.97; 95% CI: 0.94-0.99) and D LCO %pred (HR 0.97; 95% CI: 0.94-0.99) was similarly associated with all-cause mortality. There was no detectable difference in area under the curve for prediction of all-cause mortality by D LCOc %pred and D LCO %pred (C-index 0.71 and 0.72, respectively, P = 0.85 for difference). None of the defects noted on V/Q SPECT were significantly associated with mortality, but mismatched defects were associated with lower values of D LCOc %pred and D LCO %pred. D LCOc %pred and D LCO %pred perform equally as prognostic markers in PAH, supporting the use of either metric when available for prognostic stratification., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase linked to the proliferation, survival, invasion, and metastasis of several types of cancers, including colorectal cancer (CRC), particularly when aberrantly activated. Our study strategically designs peptides derived from interactions between c-Met and the antibody Onartuzumab. By utilizing a cyclic strategy, we achieved significantly enhanced peptide stability and affinity. Our in vitro assessments confirmed that the cyclic peptide HYNIC-cycOn exhibited a higher affinity ( K D = 83.5 nM) and greater specificity compared with its linear counterpart. Through in vivo experiments, [ 99m Tc]Tc-HYNIC-cycOn displayed exceptional tumor-targeting capabilities and minimal absorption in nontumor cells, as confirmed by single-photon emission computed tomography. Notably, the ratios of tumor to muscle and tumor to intestine, 1 h postinjection, were 4.78 ± 0.86 and 3.24 ± 0.47, respectively. Comparable ratios were observed in orthotopic CRC models, recording 4.94 ± 0.32 and 3.88 ± 0.41, respectively. In summary, [ 99m Tc]Tc-HYNIC-cycOn shows substantial promise as a candidate for clinical applications. We show that [ 99m Tc]Tc-HYNIC-cycOn can effectively target and visualize c-Met-expressing tumors in vivo , providing a promising approach for enhancing diagnostic accuracy when detecting c-Met in CRC.

Zolbetuximab (IMAB362), a monoclonal antibody targeting Claudin18.2 (CLDN 18.2), demonstrates a significant clinical benefit in patients with advanced gastroesophageal cancers. The noninvasive assessment of CLDN18.2 expression through molecular imaging offers a potential avenue for expedited monitoring and the stratification of patients into risk groups. This study elucidates that CLDN18.2 is expressed at a noteworthy frequency in primary gastric cancers and their metastases. The iodogen method was employed to label IMAB362 with 123 I/ 131 I. The results demonstrated the efficient and reproducible synthesis of 123 I-IMAB362, with a specific binding affinity to CLDN18.2. Immuno-single-photon emission computed tomography (SPECT) imaging revealed the rapid accumulation of 123 I-IMAB362 in gastric cancer xenografts at 12 h, remaining stable for 3 days in patient-derived tumor xenograft models. Additionally, tracer uptake of 123 I-IMAB362 in MKN45 cells surpassed that in MKN28 cells at each time point, with tumor uptake correlating significantly with CLDN18.2 expression levels. Positron emission tomography/computed tomography imaging indicated that tumor uptake of 18 F-FDG and the functional/viable tumor volume in the 131 I-IMAB362 group were significantly lower than those in the 123 I-IMAB362 group on day 7. In conclusion, 123 I-IMAB362 immuno-SPECT imaging offers an effective method for direct, noninvasive, and whole-body quantitative assessment of tumor CLDN18.2 expression in vivo. This approach holds promise for accelerating the monitoring and stratification of patients with gastric cancer.

This article report a 40-year-old male patient who underwent total thyroidectomy and forearm auto-transplantation in another hospital for secondary hyperparathyroidism. After 4 years of follow-up, the level of parathyroid hormone continued to increase, and ultrasound showed nodules in the neck and right forearm, which were considered to be of parathyroid origin. Technetium 99m sestamibi single photon emission computed tomography and computed tomography (Tc-99m-MIBI SPECT/CT) imaging showed increased radioactive uptake in the submuscular soft tissue nodule of the right medial forearm, maximum standardized uptake value (SUVmax) is 0.98, which was identified as transplanted functioning parathyroid tissue. No parathyroid imaging activity was found in the neck. The patient then underwent partial removal of ectopic parathyroid tissue from the right forearm. Pathological examination confirmed parathyroid tissue, and removal was followed by a rapid decline in serum parathyroid hormone levels., (© 2024 International Society for Hemodialysis.)

Purpose: For minimally invasive surgery of parathyroid adenomas, exact localization diagnostics are essential. Main imaging modalities used for diagnostics are sonography, SPECT with/without CT (traditional imaging) and 18 F-choline-PET. The aim of our study was to identify predictors for inconclusive SPECT imaging and subsequently determine in which cases 18 F-choline-PET is needed., Methods: Retrospective analysis of 138 patients with histologically confirmed primary hyperparathyroidism (pHPT). After sonography, patients underwent SPECT or SPECT/CT imaging, with subsequent 18 F-choline-PET in cases of disconcordant results. Logistic regression analysis was used to identify clinical and laboratory factors predictive for negative SPECT results., Results: Sensitivity rates for sonography, SPECT, SPECT/CT, and choline-PET were 47 %, 49 %, 71.7 %, and 97 %, respectively. Logistic regression revealed lower PTH levels (p < 0.001), presence of structural thyroid disease (p = 0.018), and negative sonography (p < 0.001) as predictive of negative/equivocal SPECT outcome. An additional traditional imaging CT scan to a SPECT enhanced detection odds, as did greater adenoma weight. Urolithiasis, osteoporosis, and calcium values as measurement of activity and duration of disease showed no significant association with the detection rate. Furthermore, our study demonstrated that 18 F-choline-PET exhibited remarkable sensitivity in detecting adenomas among patients with negative/equivocal SPECT results., Conclusion: Our study reveals potential predictive factors for a negative/equivocal SPECT outcome in pHPT. Identifying these factors might allow minimizing futile SPECT examinations and perhaps encourage timely utilization of 18 F-choline-PET imaging. Our study reinforces the clinical significance of 18 F-choline-PET, especially in complex cases with disconcordant results by conventional parathyroid imaging methods., Competing Interests: Declaration of competing interest M.W.H. received grants and speaker honoraria from GE Healthcare, a fund by the Alfred and Annemarie von Sick legacy and a grant from the clinical research priority program (CRPP) Artificial Intelligence in Oncological Imaging Network of the University of Zurich. Otherwise this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Spatial normalization is a prerequisite step for the quantitative analysis of SPECT or PET brain images using volume-of-interest (VOI) template or voxel-based analysis. MRI-guided spatial normalization is the gold standard, but the wide use of PET/CT or SPECT/CT in routine clinical practice makes CT-guided spatial normalization a necessary alternative. Ventricular enlargement is observed with aging, and it hampers the spatial normalization of the lateral ventricles and striatal regions, limiting their analysis. The aim of the present study was to propose a robust spatial normalization method based on CT scans that takes into account features of the aging brain to reduce bias in the CT-guided striatal analysis of SPECT images., Methods: We propose an enhanced CT-guided spatial normalization pipeline based on SPM12. Performance of the proposed pipeline was assessed on visually normal [ 123 I]-FP-CIT SPECT/CT images. SPM12 default CT-guided spatial normalization was used as reference method. The metrics assessed were the overlap between the spatially normalized lateral ventricles and caudate/putamen VOIs, and the computation of caudate and putamen specific binding ratios (SBR)., Results: In total 231 subjects (mean age ± SD = 61.9 ± 15.5 years) were included in the statistical analysis. The mean overlap between the spatially normalized lateral ventricles of subjects and the caudate VOI and the mean SBR of caudate were respectively 38.40 % (± SD = 19.48 %) of the VOI and 1.77 (± 0.79) when performing SPM12 default spatial normalization. The mean overlap decreased to 9.13 % (± SD = 1.41 %, P < 0.001) of the VOI and the SBR of caudate increased to 2.38 (± 0.51, P < 0.0001) when performing the proposed pipeline. Spatially normalized lateral ventricles did not overlap with putamen VOI using either method. The mean putamen SBR value derived from the proposed spatial normalization (2.75 ± 0.54) was not significantly different from that derived from the default SPM12 spatial normalization (2.83 ± 0.52, P > 0.05)., Conclusion: The automatic CT-guided spatial normalization used herein led to a less biased spatial normalization of SPECT images, hence an improved semi-quantitative analysis. The proposed pipeline could be implemented in clinical routine to perform a more robust SBR computation using hybrid imaging., Competing Interests: Declaration of competing interest The authors have no financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Aims: Variation in diagnostic performance of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been observed, yet the impact of cardiac size has not been well characterized. We assessed whether low left ventricular volume influences SPECT MPI's ability to detect obstructive coronary artery disease (CAD) and its interaction with age and sex., Methods and Results: A total of 2066 patients without known CAD (67% male, 64.7 ± 11.2 years) across nine institutions underwent SPECT MPI with solid-state scanners followed by coronary angiography as part of the REgistry of Fast Myocardial Perfusion Imaging with NExt Generation SPECT. Area under receiver-operating characteristic curve (AUC) analyses evaluated the performance of quantitative and visual assessments according to cardiac size [end-diastolic volume (EDV); <20th vs. ≥20th population or sex-specific percentiles], age (<75 vs. ≥75 years), and sex. Significantly decreased performance was observed in patients with low EDV compared with those without (AUC: population 0.72 vs. 0.78, P = 0.03; sex-specific 0.72 vs. 0.79, P = 0.01) and elderly patients compared with younger patients (AUC 0.72 vs. 0.78, P = 0.03), whereas males and females demonstrated similar AUC (0.77 vs. 0.76, P = 0.67). The reduction in accuracy attributed to lower volumes was primarily observed in males (sex-specific threshold: EDV 0.69 vs. 0.79, P = 0.01). Accordingly, a significant decrease in AUC, sensitivity, specificity, and negative predictive value for quantitative and visual assessments was noted in patients with at least two characteristics of low EDV, elderly age, or male sex., Conclusion: Detection of CAD with SPECT MPI is negatively impacted by small cardiac size, most notably in elderly and male patients., Competing Interests: Conflict of interest: D.S.B. and P.J.S. participated in software royalties for QPS software at Cedars-Sinai Medical Center. P.J.S. has received research grant support from Siemens Medical Systems. D.S.B., S.D., A.J.E., and E.J.M. are consultants for GE Healthcare. S.D. is a consultant for Bracco Diagnostics and has received a grant through her institution from Astellas. M.D.C. has received research grant support from Spectrum Dynamics; and he is a consultant for Sanof and GE Healthcare. D.S.B.’s institution has received grant support from HeartFlow. E.J.M. has served as a consultant for Bracco Inc, and he and his institution have received grant support from Bracco Inc. T.D.R. has received research grant support from GE Healthcare and Advanced Accelerator Applications. A.J.E. reports receiving a speaker's fee from Ionetix, consulting fees from W. L. Gore & Associates, authorship fees from Wolters Kluwer Healthcare—UpToDate, and serving on a scientific advisory board for Canon America Medical Systems USA; his institution has grants/grants pending from Attralus, BridgeBio Pharma, Canon Medical Systems USA, GE Healthcare, Intellia Therapeutics, Ionis Pharmaceuticals, Neovasc, Pfizer, Roche Medical Systems, and W. L. Gore & Associates. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Parkinson's disease (PD) is challenging for clinicians to accurately diagnose in the early stages. Quantitative measures of brain health can be obtained safely and non-invasively using medical imaging techniques like magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). For accurate diagnosis of PD, powerful machine learning and deep learning models as well as the effectiveness of medical imaging tools for assessing neurological health are required. This study proposes four deep learning models with a hybrid model for the early detection of PD. For the simulation study, two standard datasets are chosen. Further to improve the performance of the models, grey wolf optimization (GWO) is used to automatically fine-tune the hyperparameters of the models. The GWO-VGG16, GWO-DenseNet, GWO-DenseNet + LSTM, GWO-InceptionV3 and GWO-VGG16 + InceptionV3 are applied to the T1,T2-weighted and SPECT DaTscan datasets. All the models performed well and obtained near or above 99% accuracy. The highest accuracy of 99.94% and AUC of 99.99% is achieved by the hybrid model (GWO-VGG16 + InceptionV3) for T1,T2-weighted dataset and 100% accuracy and 99.92% AUC is recorded for GWO-VGG16 + InceptionV3 models using SPECT DaTscan dataset., (© 2024. The Author(s).)

Purpose: To predict side effects and optimize injection doses in the dosimetry of 177 Lu imaging, highly accurate quantitative SPECT images are required. Monte Carlo simulations were performed to verify the accuracy and variability of quantitative values for 177 Lu imaging under various imaging conditions., Methods: SPECT data of NEMA body phantom were assumed to simulate intrahepatic tumors 6 h after administration of 7.4 GBq of 177 Lu-Dotatate. SPECT data were acquired using the SIMIND program with different combinations of collimators and energy windows. For variability evaluation, 30 SPECT images with Poisson noise were generated for each acquisition time. The relative error was evaluated for accuracy evaluation, and the coefficient of variation was estimated for variability evaluation., Results: The accuracy of BG quantification was less than 10% relative error. The accuracy of hot sphere quantification was highest with the combination of MEGP and an energy window of 208 keV±10%. However, the accuracy of hot sphere quantification decreased significantly with decreasing hot sphere diameter. Variability varied with imaging conditions and improved with longer acquisition time., Conclusion: Monte Carlo simulations revealed the accuracy and variability of quantitative values for each SPECT imaging condition for 177 Lu imaging.

Images obtained from single-photon emission computed tomography for myocardial perfusion imaging (MPI SPECT) contain noises and artifacts, making cardiovascular disease diagnosis difficult. We developed a deep learning-based diagnosis support system using MPI SPECT images. Single-center datasets of MPI SPECT images (n = 5443) were obtained and labeled as healthy or coronary artery disease based on diagnosis reports. Three axes of four-dimensional datasets, resting, and stress conditions of three-dimensional reconstruction data, were reconstructed, and an AI model was trained to classify them. The trained convolutional neural network showed high performance [area under the curve (AUC) of the ROC curve: approximately 0.91; area under the recall precision curve: 0.87]. Additionally, using unsupervised learning and the Grad-CAM method, diseased lesions were successfully visualized. The AI-based automated diagnosis system had the highest performance (88%), followed by cardiologists with AI-guided diagnosis (80%) and cardiologists alone (65%). Furthermore, diagnosis time was shorter for AI-guided diagnosis (12 min) than for cardiologists alone (31 min). Our high-quality deep learning-based diagnosis support system may benefit cardiologists by improving diagnostic accuracy and reducing working hours., (© 2024. The Author(s).)

Objectives: The growing incidence of differentiated thyroid cancer (DTC) have been linked to insulin resistance and metabolic syndrome. The imperative need for developing effective diagnostic imaging tools to predict the non-iodine-avid status of lung metastasis (LMs) in differentiated thyroid cancer (DTC) patients is underscored to prevent unnecessary radioactive iodine treatment (RAI)., Methods: Primary cohort consisted 1962 pretreated LMs of 496 consecutive DTC patients with pretreated initially diagnosed LMs who underwent chest CT and subsequent post-treatment radioiodine SPECT. After automatic lesion segmentation by SE V-Net, SE Net deep learning was trained to predict non-iodine-avid status of LMs. External validation cohort contained 123 pretreated LMs of 24 consecutive patients from other two hospitals. Stepwise validation was further performed according to the nodule's largest diameter., Results: The SE-Net deep learning network yielded area under the receiver operating characteristic curve (AUC) values of 0.879 (95% confidence interval: 0.852-0.906) and 0.713 (95% confidence interval: 0.613-0.813) for internal and external validation. With the LM diameter decreasing from ≥10mm to ≤4mm, the AUCs remained relatively stable, for smallest nodules (≤4mm), the model yielded an AUC of 0.783. Decision curve analysis showed that most patients benefited using deep learning to decide radioactive I 131 treatment., Conclusion: This study presents a noninvasive, less radioactive and fully automatic approach that can facilitate suitable DTC patient selection for RAI therapy of LMs. Further prospective multicenter studies with larger study cohorts and related metabolic factors should address the possibility of comprehensive clinical transformation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gao, Chen, Wang, Xu, Zhang, Yang and Gu.)

Background and Objectives: Degeneration of the presynaptic nigrostriatal dopaminergic system is one of the main biological features of Parkinson disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which can be measured using single-photon emission CT imaging for diagnostic purposes. Despite its widespread use in clinical practice and research, the diagnostic properties of presynaptic nigrostriatal dopaminergic (DAT) imaging in parkinsonism have never been evaluated against the diagnostic gold standard of neuropathology. The aim of this study was to evaluate the diagnostic parameters of DAT imaging compared with pathologic diagnosis in patients with parkinsonism., Methods: Retrospective cohort study of patients with DAT imaging for the investigation of a clinically uncertain parkinsonism with brain donation between 2010 and 2021 to the Queen Square Brain Bank (London). Patients with DAT imaging for investigation of pure ataxia or dementia syndromes without parkinsonism were excluded. Those with a pathologic diagnosis of PD, MSA, PSP, or CBD were considered presynaptic dopaminergic parkinsonism, and other pathologies were considered postsynaptic for the analysis. DAT imaging was performed in routine clinical practice and visually classified by hospital nuclear medicine specialists as normal or abnormal. The results were correlated with neuropathologic diagnosis to calculate diagnostic accuracy parameters for the diagnosis of presynaptic dopaminergic parkinsonism., Results: All of 47 patients with PD, 41 of 42 with MSA, 68 of 73 with PSP, and 6 of 10 with CBD (sensitivity 100%, 97.6%, 93.2%, and 60%, respectively) had abnormal presynaptic dopaminergic imaging. Eight of 17 patients with presumed postsynaptic parkinsonism had abnormal scans (specificity 52.9%)., Discussion: DAT imaging has very high sensitivity and negative predictive value for the diagnosis of presynaptic dopaminergic parkinsonism, particularly for PD. However, patients with CBD, and to a lesser extent PSP (of various phenotypes) and MSA (with predominant ataxia), can show normal DAT imaging. A range of other neurodegenerative disorders may have abnormal DAT scans with low specificity in the differential diagnosis of parkinsonism. DAT imaging is a useful diagnostic tool in the differential diagnosis of parkinsonism, although clinicians should be aware of its diagnostic properties and limitations., Classification of Evidence: This study provides Class II evidence that DAT imaging does not accurately distinguish between presynaptic dopaminergic parkinsonism and non-presynaptic dopaminergic parkinsonism.

As patient exposure to ionizing radiation from medical imaging and its risks are continuing issues, this study aimed to evaluate DNA damage and repair markers after myocardial perfusion single-photon emission computed tomography (MPS). Thirty-two patients undergoing Tc-99m sestamibi MPS were studied. Peripheral blood was collected before radiotracer injection at rest and 60-90 min after injection. The comet assay (single-cell gel electrophoresis) was performed with peripheral blood cells to detect DNA strand breaks. Three descriptors were evaluated: the percentage of DNA in the comet tail, tail length, and tail moment (the product of DNA tail percentage and tail length). Quantitative PCR (qPCR) was performed to evaluate the expression of five genes related to signaling pathways in response to DNA damage and repair (ATM, ATR, BRCA1, CDKN1A, and XPC). Mann-Whitney's test was employed for statistical analysis; p < 0.05 was considered significant. Mean Tc-99m sestamibi dose was 15.1 mCi. After radiotracer injection, comparing post-exposure to pre-exposure samples of each of the 32 patients, no statistically significant differences of the DNA percentage in the tail, tail length or tail moment were found. qPCR revealed increased expression of BRCA1 and XPC, without any significant difference regarding the other genes. No significant increase in DNA strand breaks was detected after a single radiotracer injection for MPS. There was activation of only two repair genes, which may indicate that, in the current patient sample, the effects of ionizing radiation on the DNA were not large enough to trigger intense repair responses, suggesting the absence of significant DNA damage., (© 2024. The Author(s).)

Objective. Single-photon emission computed tomography (SPECT) with pinhole collimators can provide high-resolution imaging, but is often limited by low sensitivity. Acquiring projections simultaneously through multiple pinholes affords both high resolution and high sensitivity. However, the overlap of projections from different pinholes on detectors, known as multiplexing, has been shown to cause artefacts which degrade reconstructed images. Approach. Multiplexed projection sets were considered here using an analytic simulation model of AdaptiSPECT-C-a brain-dedicated multi-pinhole SPECT system. AdaptiSPECT-C has fully adaptable aperture shutters, so can acquire projections with a combination of multiplexed and non-multiplexed frames using temporal shuttering. Two strategies for reducing multiplex artefacts were considered: an algorithm to de-multiplex projections, and an alternating reconstruction strategy for projections acquired with a combination of multiplexed and non-multiplexed frames. Geometric and anthropomorphic digital phantoms were used to assess a number of metrics. Main results. Both de-multiplexing strategies showed a significant reduction in image artefacts and improved fidelity, image uniformity, contrast recovery and activity recovery (AR). In all cases, the two de-multiplexing strategies resulted in superior metrics to those from images acquired with only mux-free frames. The de-multiplexing algorithm provided reduced image noise and superior uniformity, whereas the alternating strategy improved contrast and AR. Significance. The use of these de-multiplexing algorithms means that multi-pinhole SPECT systems can acquire projections with more multiplexing without degradation of images., (© 2024 Institute of Physics and Engineering in Medicine.)

In cardiac nuclear medicine examinations, absorption in the body is the main factor in the degradation of the image quality. The Chang and external source methods were used to correct for absorption in the body. However, fundamental studies on attenuation correction for electrocardiogram (ECG)-synchronized CT imaging have not been performed. Therefore, we developed and improved an ECG-synchronized cardiac dynamic phantom and investigated the synchronized time-phase-gated attenuation correction (STPGAC) method using ECG-synchronized SPECT and CT images of the same time phase. Methods: As a basic study, SPECT was performed using synchronized time-phase-gated (STPG) SPECT and non-phase-gated (NPG) SPECT. The attenuation-corrected images were, first, CT images with the same time phase as the ECG waveform of the gated SPECT acquisition (with CT images with the ECG waveform of the CT acquisition as the reference); second, CT images with asynchronous ECG; third, CT images of the 75% region; and fourth, CT images of the 40% region. Results: In the analysis of cardiac function in the phantom experiment, left ventricle ejection fraction (heart rate, 11.5%-13.4%; myocardial wall, 49.8%-55.7%) in the CT images was compared with that in the STPGAC method (heart rate, 11.5%-13.3%; myocardial wall, 49.6%-55.5%), which was closer in value to that of the STPGAC method. In the phantom polar map segment analyses, none of the images showed variability ( F (10,10) < 0.5, P = 0.05). All images were correlated ( r = 0.824-1.00). Conclusion: In this study, we investigated the STPGAC method using a SPECT/CT system. The STPGAC method showed similar values of cardiac function analysis to the CT images, suggesting that the STPGAC method accurately reconstructed the distribution of blood flow in the myocardial region. However, the target area for attenuation correction of the heart region was smaller than that of the whole body, and changing the gated SPECT conditions and attenuation-corrected images did not affect myocardial blood flow analysis., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Bone scans, reflecting blood flow and metabolic activity in a region of interest, are frequently used to evaluate mandibular growth disorders. Increased uptake is a non-specific finding and can occur as a result of multiple causes. The correlation between radioactive tracer uptake and growth activity has not been consistently demonstrated. The aim of this study was to assess the accuracy of planar skeletal scintigraphy (SS), single-photon emission computed tomography (SPECT), and SPECT with computed tomography (CT) images (SPECT/CT) in detecting abnormal mandibular growth activity compared to clinical and radiographic/tomographic methods (reference standard) and histologic findings. A systematic review was conducted following the PRISMA guidelines. Sensitivity, specificity, and accuracy were calculated for planar SS, SPECT, and SPECT/CT. Compared to the reference standard, SPECT/CT had the best diagnostic accuracy (76.5% sensitivity, 90.4% specificity, 83.2% accuracy), followed by planar SS (81.8% sensitivity, 84.5% specificity, 83.0% accuracy) and SPECT (77.7% sensitivity, 72.4% specificity, 74.5% accuracy). The results of this study indicate that SPECT/CT has the best clinical correlation, but the certainty of the evidence is low. The differences in sensitivity and specificity between the three index tests were not clinically significant. The three tests can be useful, with only a small difference in their diagnostic value. Histopathology was found not to be satisfactory as a reference standard., Competing Interests: Declaration of Competing Interest Dr. Zachary Peacock received a travel stipend from KLS Martin group in 2022. This has no relevance or relationship to the current topic of study in the submitted manuscript. No other authors have conflicts of interest., (Copyright © 2023 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: The addition of absolute myocardial blood flow (MBF) data improves the diagnostic and prognostic accuracy of relative perfusion imaging with nuclear medicine. Cardiac-specific gamma cameras allow measurement of MBF with SPECT., Methods: This paper reviews the evidence supporting the use of SPECT to measure myocardial blood flow (MBF). Studies have evaluated SPECT MBF in large animal models and compared it in humans with invasive angiographic measurements and against the clinical standard of PET MBF. The repeatability of SPECT MBF has been determined in both single-site and multi-center trials., Results: SPECT MBF has excellent correlation with microspheres in an animal model, with the number of stenoses and fractional flow reserve, and with PET-derived MBF. The inter-user coefficient of variability is ∼20% while the COV of test-retest MBF is ∼30%. SPECT MBF improves the sensitivity and specificity of the detection of multi-vessel disease over relative perfusion imaging and provides incremental value in predicting adverse cardiac events., Conclusion: SPECT MBF is a promising technique for providing clinically valuable information in the assessment of coronary artery disease., (Copyright © 2024. Published by Elsevier Inc.)

Background: As the diagnosis of Parkinson's disease (PD) is fundamentally clinical, the usefulness of ioflupane ( 123 I) single-photon emission computed tomography (SPECT) or DaTSCAN as a diagnostic tool has been a matter of debate for years. The performance of DaTSCAN is generally recommended in the follow-up of patients with a clinically uncertain diagnosis, especially in those with a suspected essential tremor, drug-induced parkinsonism, or vascular parkinsonism. However, there is a dearth of DaTSCAN findings regarding neurodegenerative parkinsonisms besides PD and atypical parkinsonisms. To date, a specific nigrostriatal dopamine uptake pattern that would help differentiate PD from the most frequent atypical parkinsonisms is yet to be described. This fact is further complicated by the possible visualization of abnormalities in the uptake pattern in patients with rarer neurodegenerative parkinsonisms., Objectives: We aimed to summarize the current literature regarding DaTSCAN findings in patients with rare neurodegenerative parkinsonisms., Methods: The PubMed database was systematically screened for studies in English or Spanish up to October 15, 2023, using search terms "DaTSCAN", "ioflupane", "DaT-SPECT", "123I-FP-CIT SPECT", "dopamine transporter imaging", and "[123I] FP-CIT SPECT". Duplicated publications and studies regarding PD, atypical parkinsonisms, dystonia-parkinsonism, essential tremor, and parkinsonism due to non-degenerative causes were excluded., Results: The obtained results were reviewed and summarized, including DaTSCAN findings in fragile X-associated tremor/ataxia syndrome, prion diseases, Huntington's disease, spinocerebellar ataxia, hereditary spastic paraparesis, metabolic disorders, and other diseases (anti-IgLON5 disease, ring chromosome 20 syndrome, chorea-acanthocytosis, and neuronal ceroid lipofuscinosis)., Conclusions: This review highlights the need to determine in the future the utility and cost-effectiveness of DaTSCAN, both as a diagnostic and a prognostic tool, in patients with parkinsonian symptoms in rare neurodegenerative diseases., (© 2024 International Parkinson and Movement Disorder Society.)

Aim: The present study evaluated with myocardial perfusion SPECT (MPS) the diagnostic accuracy of an artificial intelligence-enabled vectorcardiography system (Cardisiography, CSG) for detection of perfusion abnormalities., Methods: We studied 241 patients, 155 with suspected CAD and 86 with known CAD who were referred for MPS. The CSG was performed after the MPS acquisition. The CSG results (1) p-factor (perfusion, 0: normal, 1: mildly, 2: moderately, 3: highly abnormal) and (2) s-factor (structure, categories as p-factor) were compared with the MPS scores. The CSG system was not trained during the study., Results: Considering the p-factor alone, a specificity of >78% and a negative predictive value of mostly >90% for all MPS variables were found. The sensitivities ranged from 17 to 56%, the positive predictive values from 4 to 38%. Combining the p- and the s-factor, significantly higher specificity values of about 90% were reached. The s-factor showed a significant correlation (p=0.006) with the MPS ejection fraction., Conclusions: The CSG system is able to exclude relevant perfusion abnormalities in patients with suspected or known CAD with a specificity and a negative predictive value of about 90% combining the p- and the s-factor. Since it is a learning system there is potential for further improvement before routine use., Competing Interests: Mr. Knobl who performed the CSG measurements receives a salary from the company Cardisio GmbH as a freelancer. The other authors declare that they have no conflicts of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

State of the art of cardiac SPECT imaging continues to advance. Contemporary clinical applications of cardiac SPECT are reviewed and illustrated. Beyond traditional stress and rest myocardial perfusion imaging, the role of digital SPECT technology, ultra low dose imaging with efficient stress first / stress only if normal imaging, deep learning algorithms relative to coronary angiography and SPECT CT, sourceless emission attenuation correction, myocardial blood flow and blood flow reserve to assess ischemic jeopardy, culprit ischemic territories, and cardiac allograft vasculopathy, advanced methods of SPECT detection of amyloid cardiomyopathy, resting MPI to define pre-operative regional scar prior to operative ablation, parametric radionuclide ventriculography to quantify dyssynchrony and benefit of biventricular pacing, assessment of treatment response of RV and LV function in patients with pulmonary hypertension, dual isotope MIBG imaging to assess cardiac risk, and the value proposition of real world effectiveness of SPECT cardiac imaging are illustrated., Competing Interests: Declaration of Competing Interest Dr. Ronald Schwartz: No disclosure, Dr. Jean-Pierre Iskandar: No disclosure, Dr. Prem Soman: Consultant, Spectrum Dynamics., (Copyright © 2024. Published by Elsevier Inc.)