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Mohammad Zobair Wardak,1 Ahmad Farid Daanish,2 Ershad Ahmad Mushkani,2 Mohammad Asif Atiq2 1Internal Medicine Specialist, Darussalam Hospital, Kabul, Afghanistan; 2Department of Pharmacology, Kabul University of Medical Sciences, Kabul, AfghanistanCorrespondence: Mohammad Asif Atiq, Department of Pharmacology, Kabul University of Medical Sciences, Kabul, Afghanistan, Tel +93777378141, Email masifatiq@gmail.comIntroduction: Previous studies have reported an association between certain medical conditions, such as hypertension and diabetes, and severe COVID-19.Objective: To determine the prevalence of hypertension and diabetes among severe COVID-19 patients who were admitted to the only specialized center for COVID-19 in Kabul, Afghan-Japan Hospital Kabul, Afghanistan.Methods: A cross-sectional design was utilized, including 202 patients, admitted to Afghan-Japan Hospital during the first six months of 2022. Medical records of patients tested positive for COVID-19 via Polymerase chain reaction (PCR) with oxygen saturation levels below 90% at the time of admission were included in the study. Age, sex, and the presence of hypertension and diabetes were the studied variables. Descriptive statistics were used for analysis.Results: The median age of the patients were 63 (IQR=54.75– 75) years. Males and females each accounting for 50% of the total, and the majority of the patients (50.5%) were in the age group 60– 79. Of 202 patients, 143 (70.8%) had hypertension, 42 (20.8%) had diabetes, 147 patients (72.77%) had at least one of these comorbidities. Fifty-five patients (27.22%) were without diabetes and without hypertension. The prevalence of hypertension and diabetes was higher among female, ie, 57.1% and 54.5% respectively. Patients in the 40– 59 year old group had the highest rate of hypertension (75.6%). The highest prevalence of diabetes was seen in the 60– 79 year old group.Conclusion: The study found a higher prevalence of hypertension in severe COVID-19 cases compared to global reports and the general adult population in Afghanistan. The relationship between hypertension and COVID-19 risk needs further investigation. The prevalence of diabetes was also higher, consistent with findings from other countries.Keywords: severe COVID-19, comorbidity, hypertension, diabetes

The aim of the present study was to evaluate the occurrence of synchronous or metachronous hematologic and gynecologic malignancies. The medical database of the pathology department at a tertiary center was searched from 2016 to 2024 for cases involving both hematologic and gynecologic tumors. A literature search using Google Scholar and PubMed was also conducted between May and June 2024. Articles reporting surgical pathology data were included, while radiologic studies and those lacking pathology data were excluded. Cases involving one gynecologic cancer and one hematologic malignancy were analyzed. Three cases from our center and 25 cases from 15 English-language articles were identified. The mean age of the cases at diagnosis was 61.4 ± 9.4 years. A total of 19 patients (68%) were diagnosed with synchronous cancers, while the rest had metachronous diagnoses. Endometrial cancer was seen in 20 cases (71.4%): 14 synchronous and five metachronous endometrioid adenocarcinomas, and one unspecified metachronous endometrial cancer. This was followed by five cases of ovarian cancer (17.9%): three synchronous serous ovarian carcinomas, one metachronous serous ovarian carcinoma, and one synchronous ovarian adenocarcinoma. Additionally, there were two cases of cervical cancer (7.1%): one synchronous adenosquamous carcinoma and one metachronous invasive squamous carcinoma, and one case of carcinosarcoma (3.6%). Involvement of more than one site is possible for hematolymphoid cancer, commonly affecting the pelvic or para-aortic lymph nodes in 16 patients (57.1%), with other sites including the cervix (4 cases, 14.3%), ovary (4 cases, 14.3%), uterus (2 cases, 7.1%), iliac/inguinal lymph nodes (2 cases, 7.1%), fallopian tube (1 case, 3.6%), vagina (1 case, 3.6%), liver (1 case, 3.6%), abdomen (1 case, 3.6%), and appendix (1 case, 3.6%). Two cases were unspecified. Non-Hodgkin lymphoma (NHL), primarily of B cell lineage, was the most common hematologic malignancy (25 cases, 89.3%, with 22 cases being B cell lineage). In contrast, Hodgkin lymphoma was observed in two cases (7.1%), and acute leukemia in one case (3.6%). Among 21 patients with available follow-up data, eight died during the follow-up period. The co-occurrence of NHL, Hodgkin lymphoma, and acute leukemia with gynecologic cancers is rare. However, during surgery for gynecologic cancers, the potential of synchronous lymphoma should be considered, particularly in cases with unusual retroperitoneal lymphadenopathy., (© 2024 International Federation of Gynecology and Obstetrics.)

Rationale : Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease characterized by dyspnea and loss of lung function. Transforming growth factor-beta (TGF-β) activation mediated by α v integrins is central to the pathogenesis of IPF. Bexotegrast (PLN 74809) is an oral, once-daily, dual-selective inhibitor of α v β 6 and α v β 1 integrins under investigation for the treatment of IPF. Positron emission tomography (PET) using an α v β 6 -specific PET tracer could confirm target engagement of bexotegrast in the lungs of participants with IPF. Objectives : This Phase 2 study (NCT04072315) evaluated α v β 6 receptor occupancy in the lung, as assessed by changes from baseline in α v β 6 PET tracer uptake, following single dose administration of bexotegrast to participants with IPF. Methods : In this open-label, single-center, single-arm study, adults with IPF received up to 2 single doses of bexotegrast, ranging from 60 to 320 mg with or without background IPF therapy (pirfenidone or nintedanib). At baseline and approximately 4 hours after each orally administered bexotegrast dose, a 60-minute dynamic PET/CT scan was conducted following administration of an α v β 6 -specific PET probe ([ 18 F]FP-R 0 1-MG-F2). α v β 6 receptor occupancy by bexotegrast was estimated from the changes in PET tracer uptake following bexotegrast. Pharmacokinetics, safety, and tolerability of bexotegrast were also assessed. Results : Eight participants completed the study. Total and unbound plasma bexotegrast concentrations increased in a dose-dependent manner, and regional PET volume of distribution (V T ) values decreased in a dose- and concentration-dependent manner. The V T data fit a simple saturation model, producing an unbound bexotegrast EC 50 estimate of 3.32 ng/mL. Estimated maximum receptor occupancy was 35%, 53%, 71%, 88%, and 92% following single 60, 80, 120, 240, and 320-mg doses of bexotegrast, respectively. No treatment-emergent adverse events related to bexotegrast were reported. Conclusions : Dose- and concentration-dependent α v β 6 receptor occupancy by bexotegrast was observed by PET imaging, supporting once-daily 160 to 320 mg dosing to evaluate efficacy in clinical trials of IPF. Trial registration number: NCT04072315 Primary source of funding: Pliant Therapeutics, Inc. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

This work describes a new electrochemical biosensor for the simultaneous determination of catechol and hydroquinone. A laccase biorecognition layer was deposited using an innovative soft plasma polymerization technique onto a multiwalled carbon nanotube (MWCNT)-modified glassy carbon electrode (GCE) to sufficiently separate catechol (CT) and hydroquinone (HQ) oxidation peaks. The electrochemical analysis carried out for MWCNTs with various morphologies was supported by density functional theory (DFT) calculations showing differences in the electronic structures of both dihydroxybenzene isomers and the MWCNTs forming the biosensor interlayer. The best biosensor peak separation and biosensor analytical parameters were observed for the device containing 75 μg of MWCNTs with a higher internal diameter. For this laccase-based biosensor, a linearity range from 0.1 to 57 μM for catechol and 0.5 to 57 μM for hydroquinone as well as a sensitivity of 0.56 and 0.54 μA/μM for catechol and hydroquinone was observed, respectively. The limit of detection (LOD) values were 0.028 and 0.15 μM for CT and HQ, respectively. This biosensor was also characterized by good selectivity, stability, and reproducibility. It was successfully applied for the quantification of contaminants in the analysis of natural water samples.

Purpose: A novel cystine-knot peptide-based PET radiopharmaceutical, 18 F-FP-R 0 1-MG-F2 (knottin), was developed to selectively bind to human integrin α v β 6 which is overexpressed in pancreatic cancer. The purpose of this study is to evaluate the safety, biodistribution, dosimetry, and lesion uptake of 18 F-FP-R 0 1-MG-F2 in patients with pancreatic cancer., Methods: Fifteen patients (6 men, 9 women) with histologically confirmed pancreatic cancer were prospectively enrolled and underwent knottin PET/CT between March 2017 and February 2021 (ClinicalTrials.gov Identifier NCT02683824). Vital signs and laboratory results were collected before and after the imaging scans. Maximum standardized uptake values (SUV max ) and mean SUV (SUV mean ) were measured in 24 normal tissues and pancreatic cancer lesions for each patient. From the biodistribution data, the organ doses and whole-body effective dose were calculated using OLINDA/EXM software., Results: There were no significant changes in vital signs or laboratory values that qualified as adverse events or serious adverse events. At 1 h post-injection, areas of high 18 F-FP-R 0 1-MG-F2 uptake included the pituitary gland, stomach, duodenum, kidneys, and bladder (average SUV mean : 9.7-14.5). Intermediate uptake was found in the normal pancreas (average SUV mean : 4.5). Mild uptake was found in the lungs and liver (average SUV mean  < 1.0). The effective dose was calculated to be 2.538 × 10 -2  mSv/MBq. Knottin PET/CT detected all known pancreatic tumors in the 15 patients, although it did not detect small peri-pancreatic lymph nodes of less than 1 cm in short diameter in two of three patients who had lymph node metastases at surgery. Knottin PET/CT detected distant metastases in the lungs (n = 5), liver (n = 4), and peritoneum (n = 2), confirmed by biopsy and/or contrast-enhanced CT., Conclusion: 18 F-FP-R 0 1-MG-F2 is a safe PET radiopharmaceutical with an effective dose comparable to other diagnostic agents. Evaluation of the primary pancreatic cancer and distant metastases with 18 F-FP-R 0 1-MG-F2 PET is feasible, but larger studies are required to define the role of this approach., Trial Registration: NCT02683824., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background The PET tracer (4S)-4-(3-[ 18 F]fluoropropyl)-l-glutamate ( 18 F-FSPG) targets the system x C - cotransporter, which is overexpressed in various tumors. Purpose To assess the role of 18 F-FSPG PET/CT in intracranial malignancies. Materials and Methods Twenty-six patients (mean age, 54 years ± 12; 17 men; 48 total lesions) with primary brain tumors ( n = 17) or brain metastases ( n = 9) were enrolled in this prospective, single-center study (ClinicalTrials.gov identifier: NCT02370563) between November 2014 and March 2016. A 30-minute dynamic brain 18 F-FSPG PET/CT scan and a static whole-body (WB) 18 F-FSPG PET/CT scan at 60-75 minutes were acquired. Moreover, all participants underwent MRI, and four participants underwent fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) PET imaging. PET parameters and their relative changes were obtained for all lesions. Kinetic modeling was used to estimate the 18 F-FSPG tumor rate constants using the dynamic and dynamic plus WB PET data. Imaging parameters were correlated to lesion outcomes, as determined with follow-up MRI and/or pathologic examination. The Mann-Whitney U test or Student t test was used for group mean comparisons. Receiver operating characteristic curve analysis was used for performance comparison of different decision measures. Results 18 F-FSPG PET/CT helped identify all 48 brain lesions. The mean tumor-to-background ratio (TBR) on the whole-brain PET images at the WB time point was 26.6 ± 24.9 (range: 2.6-150.3). When 18 F-FDG PET was performed, 18 F-FSPG permitted visualization of non- 18 F-FDG-avid lesions or allowed better lesion differentiation from surrounding tissues. In participants with primary brain tumors, the predictive accuracy of the relative changes in influx rate constant K i and maximum standardized uptake value to discriminate between poor and good lesion outcomes were 89% and 81%, respectively. There were significant differences in the 18 F-FSPG uptake curves of lesions with good versus poor outcomes in the primary brain tumor group ( P < .05) but not in the brain metastases group. Conclusion PET/CT imaging with (4S)-4-(3-[ 18 F]fluoropropyl)-l-glutamate ( 18 F-FSPG) helped detect primary brain tumors and brain metastases with a high tumor-to-background ratio. Relative changes in 18 F-FSPG uptake with multi-time-point PET appear to be helpful in predicting lesion outcomes. Clinical trial registration no. NCT02370563 © RSNA, 2022 Online supplemental material is available for this article.

Human pluripotent stem cells (PSCs), which are composed of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), provide an opportunity to advance cardiac cell therapy-based clinical trials. However, an important hurdle that must be overcome is the risk of teratoma formation after cell transplantation due to the proliferative capacity of residual undifferentiated PSCs in differentiation batches. To tackle this problem, we propose the use of a minimal noncardiotoxic doxorubicin dose as a purifying agent to selectively target rapidly proliferating stem cells for cell death, which will provide a purer population of terminally differentiated cardiomyocytes before cell transplantation. In this study, we determined an appropriate in vitro doxorubicin dose that (a) eliminates residual undifferentiated stem cells before cell injection to prevent teratoma formation after cell transplantation and (b) does not cause cardiotoxicity in ESC-derived cardiomyocytes (CMs) as demonstrated through contractility analysis, electrophysiology, topoisomerase activity assay, and quantification of reactive oxygen species generation. This study establishes a potentially novel method for tumorigenic-free cell therapy studies aimed at clinical applications of cardiac cell transplantation.

Purpose: (4S)-4-(3-[ 18 F]Fluoropropyl)- L -glutamic acid ( 18 F-FSPG) is a radiopharmaceutical for PET imaging of system x C - activity, which can be upregulated in prostate cancer. We present data on the first evaluation of patients with newly diagnosed or recurrent prostate cancer with this radiopharmaceutical., Experimental Design: Ten patients with primary and 10 patients with recurrent prostate cancer were enrolled in this prospective multicenter study. After injection of 300 MBq of 18 F-FSPG, three whole-body PET/CT scans were obtained. Visual analysis was compared with step-section histopathology when available as well as other imaging studies and clinical outcomes. Metabolic parameters were measured semiquantitatively. Expression levels of xCT and CD44 were evaluated by IHC for patients with available tissue samples., Results: 18 F-FSPG PET showed high tumor-to-background ratios with a relatively high tumor detection rate on a per-patient (89%) and per-lobe (87%) basis. The sensitivity was slightly higher with imaging at 105 minutes in comparison with 60 minutes. The maximum standardized uptake values (SUV max ) for cancer was significantly higher than both normal ( P < 0.005) and benign pathology ( P = 0.011), while there was no significant difference between normal and benign pathology ( P = 0.120). In the setting of recurrence, agreement with standard imaging was demonstrated in 7 of 9 patients (78%) and 13 of 18 lesions (72%), and revealed true local recurrence in a discordant case. 18 F-FSPG accumulation showed moderate correlation with CD44 expression., Conclusions: 18 F-FSPG is a promising tumor imaging agent for PET that seems to have favorable biodistribution and high cancer detection rate in patients with prostate cancer. Further studies are warranted to determine the diagnostic value for both initial staging and recurrence, and how it compares with other investigational radiotracers and conventional imaging modalities., (©2020 American Association for Cancer Research.)

Purpose: [ 18 F]FHBG has been used as a positron emission tomography (PET) imaging tracer for the monitoring of herpes simplex virus type 1 thymidine kinase (HSV1-tk), a reporter gene for cell and gene therapy in humans. However, this tracer shows inadequate blood-brain barrier (BBB) penetration and, therefore, would be limited for accurate quantification of reporter gene expression in the brain. Here, we report the synthesis and evaluation of 9-(4-[ 18 F]fluoro-3-(hydroxymethyl)butyl)-2(phenylthio)-6-oxopurine ([ 18 F]FHBT) as a new PET tracer for imaging reporter gene expression of HSV1-tk and its mutant HSV1-sr39tk, with the aim of improved BBB penetration., Procedures: [ 18 F]FHBT was prepared by using a tosylate precursor and [ 18 F]KF. The cellular uptake of [ 18 F]FHBT was performed in HSV1-sr39tk-positive (+) or HSV1-sr39tk-negative (-) MDA-MB-231 breast cancer cells. The specificity of [ 18 F]FHBT to assess HSV1-sr39tk expression was evaluated by in vitro blocking studies using 1 mM of ganciclovir (GCV). Penetration of [ 18 F]FHBT and [ 18 F]FHBG across the BBB was assessed by dynamic PET imaging studies in normal mice., Results: The tosylate precursor reacted with [ 18 F]KF using Kryptofix2.2.2 followed by deprotection to give [ 18 F]FHBT in 10 % radiochemical yield (decay-corrected). The uptake of [ 18 F]FHBT in HSV1-sr39tk (+) cells was significantly higher than that of HSV1-sr39tk (-) cells. In the presence of GCV (1 mM), the uptake of [ 18 F]FHBT was significantly decreased, indicating that [ 18 F]FHBT serves as a selective substrate of HSV1-sr39TK. PET images and time-activity curves of [ 18 F]FHBT in the brain regions showed similar initial brain uptakes (~ 12.75 min) as [ 18 F]FHBG (P > 0.855). Slower washout of [ 18 F]FHBT was observed at the later time points (17.75 - 57.75 min, P > 0.207)., Conclusions: Although [ 18 F]FHBT showed no statistically significant improvement of BBB permeability compared with [ 18 F]FHBG, we have demonstrated that the 2-(phenylthio)-6-oxopurine backbone can serve as a novel scaffold for developing HSV1-tk/HSV1-sr39tk reporter gene imaging agents for additional research in the future.

Purpose: (4S)-4-(3-[ 18 F]Fluoropropyl)-L-glutamic acid ([ 18 F]FSPG) measures system x C - transporter activity and shows promise for oncologic imaging. We present data on tumor uptake of this radiopharmaceutical in human subjects with head and neck cancer (HNC), colorectal cancer (CRC), and non-Hodgkin lymphoma (NHL)., Methods: A total of 15 subjects with HNC (n = 5), CRC (n = 5), or NHL (n = 5) were recruited (mean age 66.2 years, range 44-87 years). 301.4 ± 28.1 MBq (8.1 ± 0.8 mCi) of [ 18 F]FSPG was given intravenously to each subject, and 3 PET/CT scans were obtained 0-2 h post-injection. All subjects also had a positive [ 18 F]FDG PET/CT scan within 1 month prior to the [ 18 F]FSPG PET scan. Semi-quantitative and visual comparisons of the [ 18 F]FSPG and [ 18 F]FDG scans were performed., Results: [ 18 F]FSPG showed strong uptake in all but one HNC subject. The lack of surrounding brain uptake facilitated tumor delineation in the HNC patients. [ 18 F]FSPG also showed tumor uptake in all CRC subjects, but variable uptake in the NHL subjects. While the absolute [ 18 F]FDG SUV values were comparable or higher than [ 18 F]FSPG, the tumor-to-background SUV ratios were greater with [ 18 F]FSPG than [ 18 F]FDG., Conclusions: [ 18 F]FSPG PET/CT showed promising results across 15 subjects with 3 different cancer types. Concordant visualization was mostly observed between [ 18 F]FSPG and [ 18 F]FDG PET/CT images, with some inter- and intra-individual uptake variability potentially reflecting differences in tumor biology. The tumor-to-background ratios were greater with [ 18 F]FSPG than [ 18 F]FDG in the cancer types evaluated. Future studies based on larger numbers of subjects and those with a wider array of primary and recurrent or metastatic tumors are planned to further evaluate the utility of this novel tracer.

Background: H 2 15 O-positron emission tomography (PET) is considered the reference standard for absolute cerebral blood flow (CBF). However, this technique requires an arterial input function measured through continuous sampling of arterial blood, which is invasive and has limitations with tracer delay and dispersion., Purpose: To demonstrate a new noninvasive method to quantify absolute CBF with a PET/MRI hybrid scanner. This blood-free approach, called PC-PET, takes the spatial CBF distribution from a static H 2 15 O-PET scan, and scales it to the whole-brain average CBF value measured by simultaneous phase-contrast MRI., Study Type: Observational., Subjects: Twelve healthy controls (HC) and 13 patients with Moyamoya disease (MM) as a model of chronic ischemic disease., Field Strength/sequences: 3T/2D cardiac-gated phase-contrast MRI and H 2 15 O-PET., Assessment: PC-PET CBF values from whole brain (WB), gray matter (GM), and white matter (WM) in HCs were compared with literature values since 2000. CBF and cerebrovascular reactivity (CVR), which is defined as the percent CBF change between baseline and post-acetazolamide (vasodilator) scans, were measured by PC-PET in MM patients and HCs within cortical regions corresponding to major vascular territories. Statistical Tests: Linear, mixed effects models were created to compare CBF and CVR, respectively, between patients and controls, and between different degrees of stenosis., Results: The mean CBF values in WB, GM, and WM in HC were 42 ± 7 ml/100 g/min, 50 ± 7 ml/100 g/min, and 23 ± 3 ml/100 g/min, respectively, which agree well with literature values. Compared with normal regions (57 ± 23%), patients showed significantly decreased CVR in areas with mild/moderate stenosis (47 ± 17%, P = 0.011) and in severe/occluded areas (40 ± 16%, P = 0.016). Data Conclusion: PC-PET identifies differences in cerebrovascular reactivity between healthy controls and cerebrovascular patients. PC-PET is suitable for CBF measurement when arterial blood sampling is not accessible, and warrants comparison to fully quantitative H 2 15 O-PET in future studies., Level of Evidence: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;51:183-194., (© 2019 International Society for Magnetic Resonance in Medicine.)

Background and Purpose- Noninvasive imaging of brain perfusion has the potential to elucidate pathophysiological mechanisms underlying Moyamoya disease and enable clinical imaging of cerebral blood flow (CBF) to select revascularization therapies for patients. We used hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) technology to characterize the distribution of hypoperfusion in Moyamoya disease and its relationship to vessel stenosis severity, through comparisons with a normative perfusion database of healthy controls. Methods- To image CBF, we acquired [ 15 O]-water PET as a reference and simultaneously acquired arterial spin labeling (ASL) MRI scans in 20 Moyamoya patients and 15 age-matched, healthy controls on a PET/MRI scanner. The ASL MRI scans included a standard single-delay ASL scan with postlabel delay of 2.0 s and a multidelay scan with 5 postlabel delays (0.7-3.0s) to estimate and account for arterial transit time in CBF quantification. The percent volume of hypoperfusion in patients (determined as the fifth percentile of CBF values in the healthy control database) was the outcome measure in a logistic regression model that included stenosis grade and location. Results- Logistic regression showed that anterior ( P<0.0001) and middle cerebral artery territory regions ( P=0.003) in Moyamoya patients were susceptible to hypoperfusion, whereas posterior regions were not. Cortical regions supplied by arteries with stenosis on MR angiography showed more hypoperfusion than normal arteries ( P=0.001), but the extent of hypoperfusion was not different between mild-moderate versus severe stenosis. Multidelay ASL did not perform differently from [ 15 O]-water PET in detecting perfusion abnormalities, but standard ASL overestimated the extent of hypoperfusion in patients ( P=0.003). Conclusions- This simultaneous PET/MRI study supports the use of multidelay ASL MRI in clinical evaluation of Moyamoya disease in settings where nuclear medicine imaging is not available and application of a normative perfusion database to automatically identify abnormal CBF in patients.

Purpose of Review: Ischemic heart disease is caused by atherosclerosis, the build-up of plaque in the coronary arteries, which can lead to the development of heart attacks and heart muscle damage . Despite the advent of medical and surgical therapy to prevent and treat atherosclerosis and its adverse clinical effects, ischemic heart disease remains a leading cause of morbidity and mortality. Recent studies have suggested that the immune system may play a greater role in the development of plaque rupture and adverse left ventricular remodeling after myocardial infarction. Understanding the molecular processes by which inflammation contributes to the pathophysiology of ischemic heart disease is, therefore, worthwhile . This review focuses on new molecular imaging techniques to visualize immune cells to study their contribution to ischemic heart disease., Recent Findings: A common technique applied to imaging inflammation in ischemic heart disease is targeting the up-regulation and trafficking of immune cells, which may contribute to the adverse consequences associated with atherosclerosis. In the past five years, advances in cell labeling for imaging with PET and MRI, including radioisotopes and nanoparticles, have confirmed that inflammatory cells can be visualized in vivo and in greater abundance in unstable cardiovascular disease and in areas of ischemic damage. The major criticisms of these studies to date include their small sample size, lack of histological correlation, limited association with long-term outcomes, and bias toward macrophage imaging., Summary: While much progress has been made in imaging inflammation in ischemic heart disease over the past five years, additional studies in larger cohorts with histological validation and outcome correlation are needed. Nevertheless, imaging inflammation using PET or MRI has the potential to become an important adjunct tool to improve the diagnosis, risk stratification, and therapeutic monitoring of patients with ischemic heart disease., Competing Interests: Conflict of Interest All authors declare that they have no conflict of interest.

6″- 18 F-fluoromaltotriose is a PET tracer that can potentially be used to image and localize most bacterial infections, much like 18 F-FDG has been used to image and localize most cancers. However, unlike 18 F-FDG, 6″- 18 F-fluoromaltotriose is not taken up by inflammatory lesions and appears to be specific to bacterial infections by targeting the maltodextrin transporter that is expressed in gram-positive and gram-negative strains of bacteria. Methods: 6″- 18 F-fluoromaltotriose was synthesized with high radiochemical purity and evaluated in several clinically relevant bacterial strains in cultures and in living mice. Results: 6″- 18 F-fluoromaltotriose was taken up in both gram-positive and gram-negative bacterial strains. 6″- 18 F-fluoromaltotriose was also able to detect Pseudomonas aeruginosa in a clinically relevant mouse model of wound infection. The utility of 6″- 18 F-fluoromaltotriose to help monitor antibiotic therapies was also evaluated in rats. Conclusion: 6″- 18 F-fluoromaltotriose is a promising new tracer that has significant diagnostic utility, with the potential to change the clinical management of patients with infectious diseases of bacterial origin., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Head movement during a dynamic brain PET/CT imaging results in mismatch between CT and dynamic PET images. It can cause artifacts in CT-based attenuation corrected PET images, thus affecting both the qualitative and quantitative aspects of the dynamic PET images and the derived parametric images. In this study, we developed an automated retrospective image-based movement correction (MC) procedure. The MC method first registered the CT image to each dynamic PET frames, then re-reconstructed the PET frames with CT-based attenuation correction, and finally re-aligned all the PET frames to the same position. We evaluated the MC method's performance on the Hoffman phantom and dynamic FDDNP and FDG PET/CT images of patients with neurodegenerative disease or with poor compliance. Dynamic FDDNP PET/CT images (65 min) were obtained from 12 patients and dynamic FDG PET/CT images (60 min) were obtained from 6 patients. Logan analysis with cerebellum as the reference region was used to generate regional distribution volume ratio (DVR) for FDDNP scan before and after MC. For FDG studies, the image derived input function was used to generate parametric image of FDG uptake constant (Ki) before and after MC. Phantom study showed high accuracy of registration between PET and CT and improved PET images after MC. In patient study, head movement was observed in all subjects, especially in late PET frames with an average displacement of 6.92 mm. The z-direction translation (average maximum = 5.32 mm) and x-axis rotation (average maximum = 5.19 degrees) occurred most frequently. Image artifacts were significantly diminished after MC. There were significant differences (P<0.05) in the FDDNP DVR and FDG Ki values in the parietal and temporal regions after MC. In conclusion, MC applied to dynamic brain FDDNP and FDG PET/CT scans could improve the qualitative and quantitative aspects of images of both tracers.

Purpose: In this study, kinetic parameters of the cellular proliferation tracer (18)F-3'-deoxy-3'-fluoro-L-thymidine (FLT) and the amino acid probe 3,4-dihydroxy-6-(18)F-fluoro-L-phenylalanine (FDOPA) were measured before and early after the start of therapy, and were used to predict the overall survival (OS) of patients with recurrent malignant glioma using multiple linear regression (MLR) analysis., Methods: High-grade recurrent brain tumors in 21 patients (11 men and 10 women, age range 26 - 76 years) were investigated. Each patient had three dynamic PET studies with each probe: at baseline and after 2 and 6 weeks from the start of treatment. Treatment consisted of biweekly cycles of bevacizumab (an angiogenesis inhibitor) and irinotecan (a chemotherapeutic agent). For each study, about 3.5 mCi of FLT (or FDOPA) was administered intravenously and dynamic PET images were acquired for 1 h (or 35 min for FDOPA). A total of 126 PET scans were analyzed. A three-compartment, two-tissue model was applied to estimate tumor FLT and FDOPA kinetic rate constants using a metabolite- and partial volume-corrected input function. MLR analysis was used to model OS as a function of FLT and FDOPA kinetic parameters for each of the three studies as well as their relative changes between studies. An exhaustive search of MLR models using three or fewer predictor variables was performed to find the best models., Results: Kinetic parameters from FLT were more predictive of OS than those from FDOPA. The three-predictor MLR model derived using information from both probes (adjusted R(2) = 0.83) fitted the OS data better than that derived using information from FDOPA alone (adjusted R(2) = 0.41), but was only marginally different from that derived using information from FLT alone (adjusted R(2) = 0.82). Standardized uptake values (either from FLT alone, FDOPA alone, or both together) gave inferior predictive results (best adjusted R(2) = 0.25)., Conclusion: For recurrent malignant glioma treated with bevacizumab and irinotecan, FLT kinetic parameters obtained early after the start of treatment (absolute values and their associated changes) can provide sufficient information to predict OS with reasonable confidence using MLR. The slight increase in accuracy for predicting OS with a combination of FLT and FDOPA PET information may not warrant the additional acquisition of FDOPA PET for therapy monitoring in patients with recurrent glioma.

Objective: The aim of the study was to: 1) evaluate the differences in pre-post operative knee functioning, mechanical stability, isokinetic knee muscle strength in simultaneous arthroscopic patients after having undergone an anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL) with hamstring tendons reconstruction, 2) compare the results of ACL/PCL patients with the control group., Design: Controlled Laboratory Study., Materials and Methods: Results of 11 ACL/PCL patients had been matched with 22 uninjured control participants (CP). Prior to surgery, and minimum 2 years after it, functional assessment (Lysholm and IKDC 2000), mechanical knee joint stability evaluation (Lachman and "drawer" test) and isokinetic tests (bilateral knee muscle examination) had been performed. Different rehabilitation exercises had been used: isometric, passive exercises, exercises increasing the range of motion and proprioception, strength exercises and specific functional exercises., Results: After arthroscopy no significant differences had been found between the injured and uninjured leg in all isokinetic parameters in ACL/PCL patients. However, ACL/PCL patients had still shown significantly lower values of strength in relative isokinetic knee flexors (p = 0.0065) and extensors (p = 0.0171) compared to the CP. There were no differences between groups regarding absolute isokinetic strength and flexors/extensors ratio. There was statistically significant progress in IKDC 2000 (p = 0.0044) and Lysholm (p = 0.0044) scales prior to (44 and 60 points respectively) and after the reconstruction (61 for IKDC 2000 and 94 points for Lysholm)., Conclusions: Although harvesting tendons of semitendinosus and/or gracilis from the healthy extremity diminishes muscle strength of knee flexors in comparison to the CP, flexor strength had improved. Statistically significant improvement of the knee extensor function may indicate that the recreation of joint mechanical stability is required for restoring normal muscle strength. Without restoring normal muscle function and strength, surgical intervention alone may not be sufficient enough to ensure expected improvement of the articular function.

We evaluate an automated approach to the cortical surface mapping (CSM) method of VOI analysis in PET. Although CSM has been previously shown to be successful, the process can be long and tedious. Here, we present an approach that removes these difficulties through the use of 3D image warping to a common space. We test this automated method using studies of FDDNP PET in Alzheimer's disease and mild cognitive impairment. For each subject, VOIs were created, through CSM, to extract regional PET data. After warping to the common space, a single set of CSM-generated VOIs was used to extract PET data from all subjects. The data extracted using a single set of VOIs outperformed the manual approach in classifying AD patients from MCIs and controls. This suggests that this automated method can remove variance in measurements of PET data and can facilitate accurate, high-throughput image analysis.

Purpose: The primary objective of this study was to investigate whether changes in 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT) kinetic parameters, taken early after the start of therapy, could predict overall survival (OS) and progression-free survival (PFS) in patients with recurrent malignant glioma undergoing treatment with bevacizumab and irinotecan., Experimental Design: High-grade recurrent brain tumors were investigated in 18 patients (8 male and 10 female), ages 26 to 76 years. Each had 3 dynamic positron emission tomography (PET) studies as follows: at baseline and after 2 and 6 weeks from the start of treatment, ¹⁸F-FLT (2.0 MBq/kg) was injected intravenously, and dynamic PET images were acquired for 1 hour. Factor analysis generated factor images from which blood and tumor uptake curves were derived. A three-compartment, two-tissue model was applied to estimate tumor ¹⁸F-FLT kinetic rate constants using a metabolite- and partial volume-corrected input function. Different combinations of predictor variables were exhaustively searched in a discriminant function to accurately classify patients into their known OS and PFS groups. A leave-one-out cross-validation technique was used to assess the generalizability of the model predictions., Results: In this study population, changes in single parameters such as standardized uptake value or influx rate constant did not accurately classify patients into their respective OS groups (<1 and ≥ 1 year; hit ratios ≤ 78%). However, changes in a set of ¹⁸F-FLT kinetic parameters could perfectly separate these two groups of patients (hit ratio = 100%) and were also able to correctly classify patients into their respective PFS groups (<100 and ≥ 100 days; hit ratio = 88%)., Conclusions: Discriminant analysis using changes in ¹⁸F-FLT kinetic parameters early during treatment seems to be a powerful method for evaluating the efficacy of therapeutic regimens., (©2011 AACR.)

Purpose: Subcortical white matter is known to be relatively unaffected by amyloid deposition in Alzheimer's disease (AD). We investigated the use of subcortical white matter as a reference region to quantify [(18)F]FDDNP binding in the human brain., Methods: Dynamic [(18)F]FDDNP PET studies were performed on 7 control subjects and 12 AD patients. Population efflux rate constants (k(')(2)) from subcortical white matter (centrum semiovale) and cerebellar cortex were derived by a simplified reference tissue modeling approach incorporating physiological constraints. Regional distribution volume ratio (DVR) estimates were derived using Logan and simplified reference tissue approaches, with either subcortical white matter or cerebellum as reference input. Discriminant analysis with cross-validation was performed to classify control subjects and AD patients., Results: The population estimates of k(')(2) in subcortical white matter did not differ significantly between control subjects and AD patients but the variability of individual estimates of k(')(2) determined in white matter was lower than that in cerebellum. Logan DVR showed dependence on the efflux rate constant in white matter. The DVR estimates in the frontal, parietal, posterior cingulate, and temporal cortices were significantly higher in the AD group (p<0.01). Incorporating all these regional DVR estimates as predictor variables in discriminant analysis yielded accurate classification of control subjects and AD patients with high sensitivity and specificity, and the results agreed well with those using the cerebellum as the reference region., Conclusion: Subcortical white matter can be used as a reference region for quantitative analysis of [(18)F]FDDNP with the Logan method which allows more accurate and less biased binding estimates, but a population efflux rate constant has to be determined a priori.

Unlabelled: Head movement during a PET scan (especially a dynamic scan) can affect both the qualitative and the quantitative aspects of an image, making it difficult to accurately interpret the results. The primary objective of this study was to develop a retrospective image-based movement correction (MC) method and evaluate its implementation on dynamic 2-(1-{6-[(2-(18)F-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ((18)F-FDDNP) PET images of cognitively intact controls and patients with Alzheimer's disease (AD)., Methods: Dynamic (18)F-FDDNP PET images, used for in vivo imaging of beta-amyloid plaques and neurofibrillary tangles, were obtained from 12 AD patients and 9 age-matched controls. For each study, a transmission scan was first acquired for attenuation correction. An accurate retrospective MC method that corrected for transmission-emission and emission-emission misalignments was applied to all studies. No restriction was assumed for zero movement between the transmission scan and the first emission scan. Logan analysis, with the cerebellum as the reference region, was used to estimate various regional distribution volume ratio (DVR) values in the brain before and after MC. Discriminant analysis was used to build a predictive model for group membership, using data with and without MC., Results: MC improved the image quality and quantitative values in (18)F-FDDNP PET images. In this subject population, no significant difference in DVR value was observed in the medial temporal (MTL) region of controls and patients with AD before MC. However, after MC, significant differences in DVR values in the frontal, parietal, posterior cingulate, MTL, lateral temporal (LTL), and global regions were seen between the 2 groups (P < 0.05). In controls and patients with AD, the variability of regional DVR values (as measured by the coefficient of variation) decreased on average by more than 18% after MC. Mean DVR separation between controls and patients with AD was higher in frontal, MTL, LTL, and global regions after MC. Group classification by discriminant analysis based on (18)F-FDDNP DVR values was markedly improved after MC., Conclusion: The streamlined and easy-to-use MC method presented in this work significantly improves the image quality and the measured tracer kinetics of (18)F-FDDNP PET images. The proposed MC method has the potential to be applied to PET studies on patients having other disorders (e.g., Down syndrome and Parkinson's disease) and to brain PET scans with other molecular imaging probes.

Physeal changes of any aetiology in children are usually diagnosed once the deformity is clinically evident. Between January 2006 and June 2007, 15 children who suffered from acute osteoarticular infection around the knee joint were studied. They were called up for follow-up six months after the onset of infection. All patients were evaluated by clinical and roentgenographic examination before undergoing magnetic resonance imaging (MRI) study of both knees "with the unaffected knee serving as control". Abnormal findings in the physis, metaphysis and/or epiphysis on MRI were observed in five children. This group of five children was compared with the other ten children for clinical presentation and course of disease. We believe that MRI is a useful tool in the evaluation of growth plate insult in the early period following acute osteoarticular infection, and we can diagnose and prevent the catastrophic complications of the same.

Crush injuries of the foot are one of the most difficult and challenging tasks for a trauma surgeon to manage in terms of limb salvage and provision of a painless functional foot. Injuries to the foot, especially the hindfoot, account for almost 24.6% of all the warfare injuries in Afghanistan, of which more than 70% end in amputation for various reasons. We devised a method using the principles of Ilizarov's distraction osteosynthesis to salvage limbs with bony defects in the hindfoot which otherwise were candidates for amputation. The procedure is done in two stages. Initially, the ring fixator is applied for the soft tissue reconstruction and infection control, and the next stage consists of percutaneous "inverted L"-shaped osteotomy in the posterior half of the lower tibia. The study included 32 patients with hindfoot crush injuries involving talus, calcaneum, a combination of both, or even involving the adjacent tarsal bones. All these crush injuries were classified using the Gustilo and Anderson classification. The postoperative functional assessment of the feet was done using the Maryland Foot Score system with a minimum follow-up of four years. We had good results in 53%, fair in 34% and failure in 13% of our cases. The complications of this procedure were the same as with the use of the ring fixator elsewhere in the body. This method provides a technique to salvage the foot and produce a painless, stable, fused foot in one of the most difficult settings of a hindfoot crush injury.