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Abstract The effect on survival of radiographic lymph node metastasis in uterine cervical cancer patients is more important than before, even though its prognostic value not been well investigated. The aim of our study is to evaluate the prognostic potential of 18F-fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) compared with Computed Tomography (CT) in uterine cervical cancer patients with stage IIICr allocated by imaging. Fifty-five patients with biopsy-proven primary cervical cancer underwent definitive radiation therapy for stages IIB–IVB of The International Federation of Gynecology and Obstetrics (FIGO) 2018 classifications. The prognostic performance of pretreatment 18F-FDG PET and CT for assessing lymph node metastasis was evaluated by two experienced readers. The PET and CT findings were correlated with the risk of progression-free survival (PFS) and overall survival (OS). Kaplan–Meier survival curves showed that PFS was significantly worse in patients with positive lymph nodes on 18F-FDG PET than in those patients with negative lymph nodes on 18F-FDG PET (p = 0.003), whereas there was no significant difference in PFS between patients with lymph nodes sized ≥ 1 cm and those sized

Abstract Background Mature and immature teratomas are differentiated based on tumor markers and calcification or fat distribution. However, no study has objectively quantified the differences in calcification and fat distributions between these tumors. This study aimed to evaluate the diagnostic potential of CT-based textural analysis in differentiating between mature and immature teratomas in patients aged

Background: Proton beam therapy (PBT) has been recently reported to achieve excellent tumor control with minimal toxicity in patients with unresectable hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) was investigated for larger HCC. This study was designed to evaluate the therapeutic effect of PBT on unresectable HCC in comparison with TACE combined with RFA. Methods: We retrospectively analyzed 70 patients with HCC which was difficult to control by surgical resection or RFA monotherapy, 24 patients treated with PBT and 46 patients with TACE plus RFA. The therapeutic effects were assessed as local progression-free survival (PFS) and overall survival (OS). Results: The local PFS was more than 65% in 60 months for PBT and TACE plus RFA. The patients treated with PBT showed 82% OS at 60 months post-treatment. In contrast, those treated with TACE plus RFA showed 28% OS. When comparing the changes of ALBI scores in patients with different severities of chronic liver disease, the scores of PBT-treated patients were maintained at the baseline; however, those of TACE plus RFA-treated patients worsened after the treatments. Conclusions: The results indicated that PBT may show better benefits than TACE plus RFA therapy in terms of OS in patients with unresectable HCC by sparing the non-tumor liver tissues.

Background and objectivesMagnetic resonance imaging with arterial spin labeling (ASL) perfusion imaging is a noninvasive method for quantifying cerebral blood flow (CBF). We aimed to evaluate the clinical utility of ASL perfusion imaging to aid in the diagnosis of Creutzfeldt–Jakob disease (CJD).MethodsThis retrospective study enrolled 10 clinically diagnosed with probable sporadic CJD (sCJD) based on the National CJD Research & Surveillance Unit and EuroCJD criteria and 18 healthy controls (HCs). Diffusion-weighted images (DWIs), CBF images obtained from ASL, N-isopropyl-(123I)-p-iodoamphetamine (123IMP)-single-photon emission computed tomography (SPECT) images, and 18F-fluorodeoxyglucose (18FDG)-positron emission tomography (PET) images were analyzed. First, the cortical values obtained using volume-of-interest (VOI) analysis were normalized using the global mean in each modality. The cortical regions were classified into DWI-High (≥ +1 SD) and DWI-Normal (< +1 SD) regions according to the DWI-intensity values. The normalized cortical values were compared between the two regions for each modality. Second, each modality value was defined as ASL hypoperfusion (< −1 SD), SPECT hypoperfusion (< −1 SD), and PET low accumulation (< −1 SD). The overall agreement rate of DWIs with ASL-CBF, SPECT, and PET was calculated. Third, regression analyses between the normalized ASL-CBF values and normalized SPECT or PET values derived from the VOIs were performed using a scatter plot.ResultsThe mean values of ASL-CBF (N = 10), 123IMP-SPECT (N = 8), and 18FDG-PET (N = 3) in DWI-High regions were significantly lower than those in the DWI-Normal regions (p

Introduction Neuroimaging studies on attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have demonstrated differences in extensive brain structure, activity and network. However, there remains heterogeneity and inconsistency across these findings, presumably because of the diversity of the disorders themselves, small sample sizes, and site and parameter differences in MRI scanners, and their overall pathogenesis remains unclear. To address these gaps in the literature, we will apply the travelling-subject approach to correct site differences in MRI scanners and clarify brain structure and network characteristics of children with ADHD and ASD using large samples collected in a multi-centre collaboration. In addition, we will investigate the relationship between these characteristics and genetic, epigenetic, biochemical markers, and behavioural and psychological measures.Methods and analysis We will collect resting-state functional MRI (fMRI) and T1-weighted and diffusion-weighted MRI data from 15 healthy adults as travelling subjects and 300 children (ADHD, n=100; ASD, n=100; and typical development, n=100) with multi-dimensional assessments. We will also apply data from more than 1000 samples acquired in our previous neuroimaging studies on ADHD and ASD.Ethics and dissemination The study protocol has been approved by the Research Ethics Committee of the University of Fukui Hospital (approval no: 20220601). Our study findings will be submitted to scientific peer-reviewed journals and conferences.

Coronavirus disease (COVID-19) vaccination is known to cause a diagnostic dilemma due to false-positive findings on [18F]FDG PET in vaccine-associated hypermetabolic lymphadenopathy. We present two case reports of women with estrogen-receptor (ER)-positive cancer of the breast who were vaccinated for COVID-19 in the deltoid muscle. [18F]FDG positron emission tomography (PET) demonstrated primary breast cancer and multiple axillary lymph nodes with increased [18F]FDG uptake, diagnosed as vaccine-associated [18F]FDG-avid lymph nodes. Subsequent [18F]FES PET revealed single axillary lymph node metastasis in the vaccine-associated [18F]FDG-avid lymph nodes. To the best of our knowledge, this is the first study showing the usefulness of [18F]FES PET in diagnosing axillary lymph node metastasis in COVID-19-vaccinated patients harboring ER-positive breast cancer. Thus, [18F]FES PET has potential applications in the detection of true-positive metastatic lymph nodes in patients with ER-positive breast cancer regardless of the ipsilateral or contralateral side, who have received COVID-19 vaccination.

This study aimed to evaluate the renal blood flow (RBF) in patients with chronic kidney disease (CKD) using 64Cu(II)-diacetyl-bis(4-methylthiosemicarbazonate) (64Cu-ATSM) for positron emission tomography (PET)/magnetic resonance imaging (MRI). We included five healthy controls (HCs) and ten patients with CKD. The estimated glomerular filtration rate (eGFR) was calculated from the serum creatinine (cr) and cystatin C (cys) levels. The estimated RBF (eRBF) was calculated using the eGFR, hematocrit, and filtration fraction. A single dose of 64Cu-ATSM (300–400 MBq) was administered for RBF evaluation, and a 40 min dynamic PET scan was performed with simultaneous arterial spin labeling (ASL) imaging. PET-RBF images were obtained from the dynamic PET images at 3 min after injection using the image-derived input function method. The mean eRBF values calculated from various eGFR values differed significantly between the patients and HCs; both groups also differed significantly in terms of the RBF values (mL/min/100 g) measured using PET (151 ± 20 vs. 124 ± 22, p < 0.05) and ASL-MRI (172 ± 38 vs. 125 ± 30, p < 0.001). The ASL-MRI-RBF was positively correlated with the eRBFcr-cys (r = 0.858, p < 0.001). The PET-RBF was positively correlated with the eRBFcr-cys (r = 0.893, p < 0.001). The ASL-RBF was positively correlated with the PET-RBF (r = 0.849, p < 0.001). 64Cu-ATSM PET/MRI demonstrated the reliability of PET-RBF and ASL-RBF by comparing them with eRBF. This is the first study to demonstrate that 64Cu-ATSM-PET is useful for assessing the RBF and is well correlated with ASL-MRI.

This study aimed to develop a new convolutional neural network (CNN) method for estimating the specific binding ratio (SBR) from only frontal projection images in single-photon emission-computed tomography using [123I]ioflupane. We created five datasets to train two CNNs, LeNet and AlexNet: (1) 128FOV used a 0° projection image without preprocessing, (2) 40FOV used 0° projection images cropped to 40 × 40 pixels centered on the striatum, (3) 40FOV training data doubled by data augmentation (40FOV_DA, left-right reversal only), (4) 40FOVhalf, and (5) 40FOV_DAhalf, split into left and right (20 × 40) images of 40FOV and 40FOV_DA to separately evaluate the left and right SBR. The accuracy of the SBR estimation was assessed using the mean absolute error, root mean squared error, correlation coefficient, and slope. The 128FOV dataset had significantly larger absolute errors compared to all other datasets (p < 0. 05). The best correlation coefficient between the SBRs using SPECT images and those estimated from frontal projection images alone was 0.87. Clinical use of the new CNN method in this study was feasible for estimating the SBR with a small error rate using only the frontal projection images collected in a short time.

Abstract Background Preoperative accurate assessment of endometrial cancer can assist in the planning of additional surgical options, and in predicting the prognosis. The aim of the present study was to evaluate the diagnostic potential of non-contrast PET/MRI with 18F-fluorodeoxyglucose (18F-FDG) for assessment in preoperative staging of endometrial cancer. Methods Thirty-six patients with biopsy-proven endometrial cancer underwent preoperative 18F-FDG PET/MRI, contrast-enhanced CT (ceCT) and pelvic dynamic contrast-enhanced MRI (ceMRI) for initial staging. The diagnostic performance of 18F-FDG PET/MRI and ceMRI for assessing the extent of the primary tumor (T stage), and 18F-FDG PET/MRI and ceCT for assessing nodal (N stage) and distant (M stage) metastasis, was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. The McNemar test was employed for statistical analysis. Results Accuracy for T status was 77.8 and 75.0% for 18F-FDG PET/MRI and ceMRI, respectively. Patient-based accuracy for detecting regional nodal and distant metastasis was 91.3 and 81.8% for 18F-FDG PET/MRI, and 87.0 and 81.8% for ceCT. None of these parameters was statistically significant (p > 0.05). Lesion-based sensitivity, specificity and accuracy for detecting regional nodal metastasis were 100, 96.9 and 97.0% for 18F-FDG PET/MRI, and 14.3, 97.6 and 93.3% for ceCT; sensitivity was statistically significant (p

Abstract Purpose To evaluate the diagnostic potential of PET/MRI with 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) in ovarian cancer. Materials and methods Participants comprised 103 patients with suspected ovarian cancer underwent pretreatment [18F]FDG PET/MRI, contrast-enhanced CT (ceCT) and pelvic dynamic contrast-enhanced MRI (ceMRI). Diagnostic performance of [18F]FDG PET/MRI and ceMRI for assessing the characterization and the extent of the primary tumor (T stage) and [18F]FDG PET/MRI and ceCT for assessing nodal (N stage) and distant (M stage) metastases was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. The McNemar test was employed for statistical analysis. Results Accuracy for the characterization of suspected ovarian cancer was significantly better for [18F]FDG PET/MRI (92.5%) [95% confidence interval (CI) 0.84–0.95] than for ceMRI (80.6%) (95% CI 0.72–0.83) (p

Abstract Background Multimodal PET/MRI image data simultaneously obtained from patients with early-stage of Alzheimer’s disease (eAD) were assessed in order to observe pathophysiologic and functional changes, as well as alterations of morphology and connectivity in the brain. Fifty-eight patients with mild cognitive impairment and early dementia (29 males, 69 ± 12 years) underwent [11C]Pittsburgh compound-B (PiB) PET/MRI with 70-min PET and MRI scans. Sixteen age-matched healthy controls (CTL) (9 males, 68 ± 11 years) were also studied with the same scanning protocol. Cerebral blood flow (CBF) was calculated from the early phase PET images using the image-derived input function method. A standardized uptake value ratio (SUVr) was calculated from 50 to 70 min PET data with a reference region of the cerebellar cortex. MR images such as 3D-T1WI, resting-state functional MRI (RS-fMRI), diffusion tensor image (DTI), and perfusion MRI acquired during the dynamic PET scan were also analyzed to evaluate various brain functions on MRI. Results Twenty-seven of the 58 patients were determined as eAD based on the results of PiB-PET and clinical findings, and a total of 43 subjects’ data including CTL were analyzed in this study. PiB SUVr values in all cortical regions of eAD were significantly greater than those of CTL. The PiB accumulation intensity was negatively correlated with cognitive scores. The regional PET-CBF values of eAD were significantly lower in the bilateral parietal lobes and right temporal lobe compared with CTL, but not in MRI perfusion; however, SPM showed regional differences on both PET- and MRI-CBF. SPM analysis of RS-fMRI delineated regional differences between the groups in the anterior cingulate cortex and the left precuneus. VBM analysis showed atrophic changes in the AD group in a part of the bilateral hippocampus; however, analysis of fractional anisotropy calculated from DTI data did not show differences between the two groups. Conclusion Multimodal analysis conducted with various image data from PiB-PET/MRI scans showed differences in regional CBF, cortical volume, and neuronal networks in different regions, indicating that pathophysiologic and functional changes in the AD brain can be observed from various aspects of neurophysiologic parameters. Application of multimodal brain images using PET/MRI would be ideal for investigating pathophysiologic changes in patients with dementia and other neurodegenerative diseases.

We investigated the relationship between MRI-arterial spin labeling (ASL) parameters and PET-cerebral blood flow (CBF)/cerebrovascular reactivity (CVR) simultaneously obtained by PET/MRI in Moyamoya disease. Twelve patients underwent 15O-water PET/MRI with the acetazolamide (ACZ) challenge test. PET-CBF and PET-CVR were measured using 15O-water PET. Pseudo-continuous ASL obtained the robust arterial transit time (ATT) and ASL-CBF estimation. ASL parameters were compared with PET-CBF and PET-CVR. Before ACZ loading, absolute and relative ASL-CBF were significantly correlated with absolute and relative PET-CBF (r = 0.44, p < 0.0001, and r = 0.55, p < 0.0001, respectively). After ACZ loading, absolute and relative ASL-CBF were significantly correlated with absolute and relative PET-CBF (r = 0.56, p < 0.001, and r = 0.75, p < 0.0001, respectively), and ΔASL-CBF was significantly correlated with ΔPET-CBF (r = 0.65, p < 0.0001). Baseline ASL-ATT had strong negative correlations with ΔPET-CBF and PET-CVR (r = −0.72, p < 0.0001, and r = −0.66, p < 0.0001, respectively). Baseline ASL-ATT of MCA territories with CVR 30% (898 ± 197 ms). ASL-ATT ratio of MCA territories with CVR < 30% (94.0 ± 10.5%) was significantly higher than that with CVR > 30% (81.4 ± 11.3%). ATT correction using multiple postlabeling delays increased the accuracy of ASL-CBF quantitation. Baseline ASL-ATT is a hemodynamic parameter and may represent an efficient alternative to PET-CVR.

Background Anti-programmed death-1 (anti-PD-1) therapy has shown clinical success in patients with advanced non-small cell lung cancer (NSCLC). However, it is difficult to evaluate the early response to anti-PD-1 therapy. We determined whether changes in 3′-deoxy-3′-[18F]-fluorothymidine (18F-FLT) PET parameters before and soon after treatment initiation predicted the therapeutic effect of anti-PD-1 antibody.Methods Twenty-six patients with advanced NSCLC treated with anti-PD-1 antibody were enrolled prospectively and underwent 18F-FLT PET before and at 2 and 6 weeks after treatment initiation. Changes in maximal standardized uptake value (ΔSUVmax), proliferative tumor volume (ΔPTV) and total lesion proliferation (ΔTLP) of the lesions were calculated and evaluated for their associations with the clinical response to therapy.Results The disease control rate was 64%. Patients with non-progressive disease (non-PD) had significantly decreased TLP at 2 weeks, and decreased SUVmax, PTV, and TLP at 6 weeks, compared with those with PD, while three of eight (37.5%) patients who responded had increased TLP from baseline at 2 weeks (ie, pseudoprogression). Among the parameters that changed between baseline and 2 weeks, ΔPTV0-2 and ΔTLP0-2 had the highest accuracy (76.0%) to predict PD. Among the parameters that changed between baseline and 6 weeks, ΔSUVmax0-6, ΔPTV0-6 and ΔTLP0-6 had the highest accuracy (90.9%) to predict PD. ΔTLP0-2 (≥60%, HR 3.41, 95% CI 1.34–8.65, p=0.010) and ΔTLP0-6 (≥50%, HR 31.4, 95% CI 3.55 to 276.7, p=0.0019) were indicators of shorter progression-free survival.Conclusions Changes in 18F-FLT PET parameters may have value as an early predictive biomarker for the response to anti-PD-1 therapy in patients with NSCLC. However, it should be noted that pseudoprogression was observed in 18F-FLT PET imaging at 2 weeks after treatment initiation.Trial registration number jRCTs051180147.

Abstract Background Accurate attenuation correction (AC) is one of the most important issues to be addressed in quantitative brain PET/MRI imaging. Atlas-based MRI AC (AB-MRAC), one of the representative MRAC methods, has been used to estimate the skull attenuation in brain scans. The zero echo time (ZTE) pulse sequence is also expected to provide a better MRAC estimation in brain PET scans. The difference in quantitative measurements of cerebral blood flow (CBF) using H2 15O-PET/MRI was compared between the two MRAC methods, AB and ZTE. Method Twelve patients with cerebrovascular disease (4 males, 43.2 ± 11.7 years) underwent H2 15O-PET/MRI studies with a 3-min PET scan and MRI scans including the ZTE sequence. Eleven of them were also studied under the conditions of baseline and 10 min after acetazolamide administration, and 2 of them were followed up after several months interval. A total of 25 PET images were reconstructed as dynamic data using 2 sets of reconstruction parameters to obtain the image-derived input function (IDIF), the time-activity curves of the major cerebral artery extracted from images, and CBF images. The CBF images from AB- and ZTE-MRAC were then compared for global and regional differences. Results The mean differences of IDIF curves at each point obtained from AB- and ZTE-MRAC dynamic data were less than 5%, and the differences in time-activity curves were very small. The means of CBF from AB- and ZTE-MRAC reconstructions calculated using each IDIF showed differences of less than 5% for all cortical regions. CBF images from AB-MRAC tended to show greater values in the parietal region and smaller values in the skull base region. Conclusion The CBF images from AB- and ZTE-MRAC reconstruction showed no significant differences in regional values, although the parietal region tended to show greater values in AB-MRAC reconstruction. Quantitative values in the skull base region were very close, and almost the same IDIFs were obtained.

Abstract Background Bone marrow failure syndrome (BMFS) is a heterogeneous group of disorders associated with single- or multiple-lineage cytopenia and failure of normal hematopoiesis. We assessed the feasibility of integrated PET/MRI with 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) to assess the pathophysiology of whole-body bone marrow for the diagnosis and monitoring of BMFS. Twenty-five consecutive patients with BMFS underwent a pre-treatment 18F-FLT PET/MRI scan. They included 7 patients with aplastic anemia (AA), 16 with myelodysplastic syndrome (MDS), and 2 with myeloproliferative neoplasms (MPNs), primary myelofibrosis (MF), and secondary [post-essential thrombocythemia (post-ET)] MF. Two of the seven AA patients underwent a post-treatment scan. Eight of the 16 MDS patients who exhibited decreased 18F-FLT uptake in the pelvis were considered to have hypoplastic MDS (hypo-MDS). 18F-FLT PET and diffusion-weighted imaging (DWI) were visually and quantitatively evaluated. Results The 18F-FLT uptake in the ilium was strongly correlated with bone marrow cellularity based on biopsy samples (ρ = 0.85). AA patients exhibited heterogeneously decreased uptake of 18F-FLT according to disease severity. Multiple 18F-FLT foci were observed in the proximal extremities, and they were in the central skeleton in severe AA patients. Post-treatment 18F-FLT PET scans of severe AA patients reflected the response of hematopoietic activity to treatment. MDS patients had marked 18F-FLT uptake in the central skeleton and proximal extremities, whereas hypo-MDS patients had heterogeneously decreased uptake, similar to that of non-severe AA patients. 18F-FLT PET and DWI were unable to predict the progression to leukemia for both MDS and hypo-MDS patients. A primary MF patient had slightly decreased 18F-FLT uptake in the central skeleton, but marked expansion of bone marrow activity to the distal extremities and high uptake of tracer in the extremely enlarged spleen (extramedullary hematopoiesis). In contrast, a secondary (post-ET) MF patient demonstrated marked bone marrow uptake, reflecting the hypercellular marrow with fibrosis. DWI revealed diffusely high signal intensities in both the primary and secondary MF patients. Conclusion 18F-FLT PET can be used to noninvasively assess whole-body bone marrow proliferative activity and DWI may reflect the different aspects of bone marrow pathophysiology from 18F-FLT PET. 18F-FLT PET/MRI is useful for the diagnosis and monitoring of BMFS, except for the differentiation between non-severe AA and hypo-MDS, and the prediction of progression to leukemia.

Background: In clinical practice, equivocal findings are inevitable in visual interpretation of whether amyloid positron emission tomography (PET) is positive or negative. It is therefore necessary to establish a more objective quantitative evaluation method for determining the indication for disease-modifying drugs currently under development.Aims: We aimed to determine cutoffs for positivity in quantitative analysis of 18F-flutemetamol PET in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also evaluated the clinical efficacy of amyloid PET in the diagnosis of AD. This study was registered in the Japan Registry of Clinical Trials (jRCTs, 031180321).Methods: Ninety-three patients suspected of having AD underwent 18F-flutemetamol PET in seven institutions. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by two board-certified nuclear medicine physicians. If the two readers obtained different interpretations, the visual rating was rerun until they reached consensus. The PET images were quantitatively analyzed using the standardized uptake value ratio (SUVR) and standardized Centiloid (CL) scale with the whole cerebellum as a reference area.Results: Visual interpretation obtained 61 positive and 32 negative PET scans. Receiver operating characteristic analysis determined the best agreement of quantitative assessments and visual interpretation of PET scans to have an area under curve of 0.982 at an SUVR of 1.13 and a CL of 16. Using these cutoff values, there was high agreement between the two approaches (kappa = 0.88). Five discordant cases had SUVR and CL values ranging from 1.00 to 1.22 and from 1 to 26, respectively. In these discordant cases, either diffuse or mildly focal elevation of cortical activity confused visual interpretation. The amyloid PET outcome significantly altered the diagnosis of AD (χ2 = 51.3, p < 0.0001). PET imaging elevated the proportions of the very high likelihood category from 20.4 to 46.2% and the very low likelihood category from 0 to 22.6%.Conclusion: Quantitative analysis of amyloid PET using 18F-flutemetamol can objectively evaluate amyloid positivity using the determined cutoffs for SUVR and CL. Moreover, amyloid PET may have added value over the standard diagnostic workup in dementia patients with cognitive impairment and suspected AD.

Oxidative stress imaging using diacetyl-bis (N4-methylthiosemicarbazone) (Cu-ATSM) was applied to the evaluation of patients with early Alzheimer’s disease (eAD). Ten eAD patients (72 ± 9 years) and 10 age-matched healthy controls (HCs) (73 ± 9 years) participated in this study. They underwent dynamic PET/MRI using 11C-PiB and 64Cu-ATSM with multiple MRI sequences. To evaluate cerebral oxidative stress, three parameters of 64Cu-ATSM PET were compared: standardized uptake value (SUV), tracer influx rate (Kin), and a rate constant k3. The input functions were estimated by the image-derived input function method. The relative differences were analyzed by statistical parametric mapping (SPM) using SUV and Kin images. All eAD patients had positive and HC subjects had negative PiB accumulation, and MMSE scores were significantly different between them. The 64Cu-ATSM accumulation tended to be higher in eAD than in HCs for both SUV and Kin. When comparing absolute values, eAD patients had a greater Kin in the posterior cingulate cortex and a greater k3 in the hippocampus compared with lobar cortical values of HCs. In SPM analysis, eAD had an increased left operculum and decreased bilateral hippocampus and anterior cingulate cortex compared to HCs. 64Cu-ATSM PET/MRI and tracer kinetic analysis elucidated cerebral oxidative stress in the eAD patients, particularly in the cingulate cortex and hippocampus.

Background The early response to treatment with immune-checkpoint inhibitors is difficult to evaluate. We determined whether changes in integrated [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/MRI (18F-FDG PET/MRI) parameters after the first 2 weeks of antiprogrammed death-1 antibody nivolumab therapy could predict the response of patients with non-small cell lung cancer (NSCLC).Methods Twenty-five patients with previously treated NSCLC were enrolled prospectively and underwent 18F-FDG PET/MRI before and at 2 weeks after nivolumab therapy. Changes in maximal standardized uptake value, total lesion glycolysis (ΔTLG) and apparent diffusion coefficient (ΔADC) between the two scans were calculated and evaluated for their associations with the clinical response to therapy.Results The disease control rate was 64%. Patients with non-progressive disease (non-PD) had significantly decreased TLG, increased ADCmean (ie, negative ΔADCmean) and lower ΔTLG+ΔADCmean than patients with PD. Among the parameters tested, receiver operating characteristic curve analysis revealed that a cut-off value of 16.5 for ΔTLG+ΔADCmean had the highest accuracy (92%) for distinguishing between patients with non-PD and PD. A ΔTLG+ΔADCmean value

To clarify the differences in hemodynamic status between atherosclerotic steno-occlusive lesions (SOL) and moyamoaya disease (MMD), hemodynamic parameters were compared using 15O-PET. Twenty-four patients with unilateral SOL (67 ± 11 y) and eighteen with MMD (33 ± 16 y) were assigned to this study. MMD patients were divided into twelve unilateral and six bilateral lesions. All patients underwent 15O-PET to measure cerebral blood flow (CBF), blood volume (CBV), oxygen extraction fraction (OEF), and metabolic rate (CMRO2). Acetazolamide was administered after the baseline scan and the second 15O-water PET was performed to evaluate cerebrovascular reactivity (CVR). For the CBF calculation in 15O-water PET, the three-weighted integral method was applied based on a one-tissue compartment model with pixel-by-pixel delay correction to measure precise CBF and arterial-to-capillary blood volume (V0). Baseline hemodynamic parameters showed significantly lower CBF, V0, and CMRO2, but greater CBV, OEF, and delay (p < 0.01) in the affected hemispheres than in the unaffected hemispheres. After ACZ administration, both hemispheres showed a significant increase in CBF (p < 0.0001), but not in V0. CVR differed significantly between the hemispheres. The arterial perfusion pressure of the functioning arterial part tended to be reduced after acetazolamide administration in patients with past neurologic events caused by hemodynamic impairment. MMD patients showed greater inactive vascular and venous volumes compared with common atherosclerotic SOL patients. The hemodynamic status of cerebral circulation may vary according to the chronic process of steno-occlusive change and the development of collateral circulation. In order to evaluate physiologic differences between the two diseases, 15O-PET with an acetazolamide challenge test is useful.

Purpose: To evaluate the diagnostic potential of PET/MRI with 18F-fluorodeoxyglucose (18F-FDG) in cervical cancer based on the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. Materials and Methods: Seventy-two patients with biopsy-proven primary cervical cancer underwent pretreatment 18F-FDG PET/MRI, CT, and pelvic MRI. The diagnostic performance of 18F-FDG PET/MRI and MRI for assessing extent of the primary tumor and 18F-FDG PET/MRI and CT for assessing nodal and distant metastases was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. McNemar test was employed for statistical analysis. Results: Accuracy for the invasion of vagina, parametrium, side wall, and adjacent organs was 97.2%, 93.1%, 97.2%, and 100% for 18F-FDG PET/MRI; and 97.2%, 91.7%, 97.2%, and 100% for pelvic MRI, respectively (p > 0.05). Patient-based accuracy for metastasis to pelvic and paraaortic lymph nodes and distant organs was 95.8%, 98.6%, and 100% for 18F-FDG PET/MRI; and 83.3%, 95.8%, and 97.2% for CT, respectively; metastasis to pelvic lymph nodes was statistically significant (p < 0.01). Lesion-based sensitivity, specificity, and accuracy for lymph nodes were 83.3%, 95.9%, and 94.8% for 18F-FDG PET/MRI; and 29.2%, 98.9% and 93.1% for CT, respectively; sensitivity was statistically significant (p < 0.001). After excluding patients diagnosed by conization, accuracy for revised FIGO staging 2018 was significantly better for 18F-FDG PET/MRI (82.1%) than for CT and MRI (60.7%) (p < 0.01). Conclusions: 18F-FDG PET/MRI offers higher diagnostic value for revised 2018 FIGO staging, suggesting that 18F-FDG PET/MRI might provide an optimal diagnostic strategy for preoperative staging.

A noninvasive image-derived input function (IDIF) method using PET/MRI was applied to quantitative measurements of [11C] Pittsburgh compound-B (PiB) distribution volume (DV) and compared with other metrics. Fifty-three patients suspected of early dementia (71 ± 11 y) underwent 70 min [11C]PiB PET/MRI. Nineteen of them (68 ± 11 y) without head motion during the scan were enrolled in this study and compared with 16 age-matched healthy controls (CTL: 68 ± 11 y). The dynamic frames reconstructed from listmode PET data were used for DV calculation. IDIF with metabolite correction was applied to the Logan plot method, and DV was normalized into DV ratio (DVR) images using the cerebellar reference (DVRL). DVR and standardized uptake value ratio (SUVR) images were also calculated using the reference tissue graphical method (DVRr) and the 50–70 min static data with cerebellar reference, respectively. Cortical values were compared using the 3D-T1WI MRI segmentation. All patients were assigned to the early Alzheimer’s disease (eAD) group because of positive [11C]PiB accumulation. The correlations of regional values were better for DVRL vs. DVRr (r2 = 0.97) than for SUVR vs. DVRr (r2 = 0.88). However, all metrics clearly differentiated eAD from CTL with appropriate thresholds. Noninvasive quantitative [11C]PiB PET/MRI measurement provided equivalent DVRs with the two methods. SUVR images showed acceptable results despite inferior variability and image quality to DVR images.

A fully automatic method for specific binding ratio (SBR) calculation in [123I]ioflupane single-photon emission computed tomography (SPECT) studies was proposed by creating volumes of interest of the striatum (VOIst) and reference region (VOIref) without manual handling to avoid operator-induced variability. The study involved 105 patients (72 ± 10 years) suspected of parkinsonian syndrome (PS) who underwent [123I]ioflupane SPECT. The 200 images from our previous study were used for evaluation and validation of the new program. All patients were classified into PS and non-PS groups according to the results of clinical follow-up. A trapezoidal volume of interest (VOIt) containing all striatal intensive counts was created automatically, followed by VOIst setting using the previous method. SBR values were calculated from the mean values of VOIst and VOIref determined by the whole brain outside of VOIt. The low count voxels in the VOIref were excluded using an appropriate threshold. The SBR values from the new method were compared with the previous semi-automatic method and the Tossici–Bolt (TB) method. The SBRs from the semi- and fully automatic methods showed a good linear correlation (r > 0.98). The areas under the curves (AUCs) of receiver operating characteristic analysis showed no significant difference between the two methods for both our previous (AUC > 0.99) and new (AUC > 0.95) data. The diagnostic accuracy of the two methods showed similar results (>92%), and both were better than the TB method. The proposed method successfully created the automatic VOIs and calculated SBR rapidly (9 ± 1 s/patient), avoiding operator-induced variability and providing objective SBR results.

Arterial transit time (ATT) is most crucial for measuring absolute cerebral blood flow (CBF) by arterial spin labeling (ASL), a noninvasive magnetic resonance (MR) perfusion assessment technique, in patients with chronic occlusive cerebrovascular disease. We validated ASL-CBF and ASL-ATT maps calculated by pulsed continuous ASL (pCASL) with multiple post-label delay acquisitions in patients with occlusive cerebrovascular disease. Fifteen patients underwent MR scans, including pCASL, and positron emission tomography (PET) scans with 15O-water to obtain PET-CBF. MR acquisitions with different post-label delays (1.0, 1.5, 2.0, 2.5 and 3.0 sec) were also obtained for ATT correction. The theoretical framework of 2-compartmental model (2CM) was also used for the delay compensation. ASL-CBF and ASL-ATT were calculated based on the proposed 2CM, and the effect on the CBF values and the ATT correction characteristics were discussed. Linear regression analyses were performed both on pixel-by-pixel and region-of-interest bases in the middle cerebral artery (MCA) territory. There were significant correlations between ASL-CBF and PET-CBF both for voxel values (r = 0.74 ± 0.08, slope: 0.87 ± 0.22, intercept: 6.1 ± 4.9) and for the MCA territorial comparison in both affected (R2 = 0.67, y = 0.83x + 6.3) and contralateral sides (R2 = 0.66, y = 0.74x + 6.3). ASL-ATTs in the affected side were significantly longer than those in the contralateral side (1.51 ± 0.41 sec and 1.12 ± 0.30 sec, respectively, p

PURPOSE:Tumor redox is an important factor for cancer progression, resistance to treatments, and a poor prognosis. The aim of the present study was to define tumor redox (over-reduction) using 62Cu-diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) PET and compare its prognostic potential in head and neck cancer (HNC) with that of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). METHODS:Thirty HNC patients (stage II-IV) underwent pretreatment 62Cu-ATSM and 18F-FDG PET scans. Maximum standardized uptake values (SUVATSM and SUVFDG) and tumor-to-muscle activity concentration ratios (TMRATSM and TMRFDG) were measured. Reductive-tumor-volume (RTV) was then determined at four thresholds (40%, 50%, 60%, and 70% SUVATSM), and total-lesion-reduction (TLR) was calculated as the product of the mean SUV and RTV for 62Cu-ATSM. In 18F-FDG, metabolic-tumor-volume (MTV) and total-lesion-glycolysis (TLG) were obtained at a threshold of 40%. A ROC analysis was performed to determine % thresholds for RTV and TLR showing the best predictive performance, and these were then used to determine the optimal cut-off values to stratify patients for each parameter. Progression-free-survival (PFS) and cause-specific-survival (CSS) were evaluated by the Kaplan-Meier method. RESULTS:The means ± standard deviations of PFS and CSS periods were 16.4±13.4 and 19.2±12.4 months, respectively. A ROC analysis determined that the 70% SUVATSM threshold for RTV and TLR was the best for predicting disease progression and cancer death. Optimal cut-offs for each index were SUVATSM = 3.6, SUVFDG = 7.9, TMRATSM = 3.2, TMRFDG = 5.6, RTV = 2.9, MTV = 8.1, TLR = 14.0, and TLG = 36.5. When the cut-offs for TMRATSM and TLR were set as described above in 62Cu-ATSM PET, patients with higher TMRATSM (p = 0.03) and greater TLR (p = 0.02) showed significantly worse PFS, while patients with greater TLR had significantly worse CSS (p = 0.02). Only MTV in 18F-FDG PET predicted differences in PSF and CSS (p = 0.03 and p = 0.03, respectively). CONCLUSION:Tumor redox parameters measured by 62Cu-ATSM PET may be determinants of HNC patient outcomes and help define optimal patient-specific treatments.