Thin-slice 2D MR Imaging of the Shoulder Joint Using Denoising Deep Learning Reconstruction Provides Higher Image Quality Than 3D MR Imaging

PURPOSE: This study was conducted to evaluate whether thin-slice 2D fat-saturated proton density-weighted images of the shoulder joint in three imaging planes combined with parallel imaging, partial Fourier technique, and denoising approach with deep learning-based reconstruction (dDLR) are more useful than 3D fat-saturated proton density multi-planar voxel images. METHODS: Eighteen patients who underwent MRI of the shoulder joint at 3T were enrolled. The denoising effect of dDLR in 2D was evaluated using coefficient of variation (CV). Qualitative evaluation of anatomical structures, noise, and artifacts in 2D after dDLR and 3D was performed by two radiologists using a five-point Likert scale. All were analyzed statistically. Gwet's agreement coefficients were also calculated. RESULTS: The CV of 2D after dDLR was significantly lower than that before dDLR (P < 0.05). Both radiologists rated 2D higher than 3D for all anatomical structures and noise (P < 0.05), except for artifacts. Both Gwet's agreement coefficients of anatomical structures, noise, and artifacts in 2D and 3D produced nearly perfect agreement between the two radiologists. The evaluation of 2D tended to be more reproducible than 3D. CONCLUSION: 2D with parallel imaging, partial Fourier technique, and dDLR was proved to be superior to 3D for depicting shoulder joint structures with lower noise.

Thin-slice reverse encoding distortion correction DWI facilitates visualization of non-functioning pituitary neuroendocrine tumor (PitNET)/pituitary adenoma and surrounding normal structures.

BACKGROUND: To evaluate the clinical usefulness of thin-slice echo-planar imaging (EPI)-based diffusion-weighted imaging (DWI) with an on-console distortion correction technique, termed reverse encoding distortion correction DWI (RDC-DWI), in patients with non-functioning pituitary neuroendocrine tumor (PitNET)/pituitary adenoma. METHODS: Patients with non-functioning PitNET/pituitary adenoma who underwent 3-T RDC-DWI between December 2021 and September 2022 were retrospectively enrolled. Image quality was compared among RDC-DWI, DWI with correction for distortion induced by B0 inhomogeneity alone (B0-corrected-DWI), and original EPI-based DWI with anterior-posterior phase-encoding direction (AP-DWI). Susceptibility artifact, anatomical visualization of cranial nerves, overall tumor visualization, and visualization of cavernous sinus invasion were assessed qualitatively. Quantitative assessment of geometric distortion was performed by evaluation of anterior and posterior displacement between each DWI and the corresponding three-dimensional T2-weighted imaging. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient values were measured. RESULTS: Sixty-four patients (age 70.8 ± 9.9 years [mean ± standard deviation]; 33 females) with non-functioning PitNET/pituitary adenoma were evaluated. In terms of susceptibility artifacts in the frontal and temporal lobes, visualization of left trigeminal nerve, overall tumor visualization, and anterior displacement, RDC-DWI performed the best and B0-corrected-DWI performed better than AP-DWI. The right oculomotor and right trigeminal nerves were better visualized by RDC-DWI than by B0-corrected-DWI and AP-DWI. Visualization of cavernous sinus invasion and posterior displacement were better by RDC-DWI and B0-corrected-DWI than by AP-DWI. SNR and CNR were the highest for RDC-DWI. CONCLUSIONS: RDC-DWI achieved excellent image quality regarding susceptibility artifact, geometric distortion, and tumor visualization in patients with non-functioning PitNET/pituitary adenoma. RELEVANCE STATEMENT: RDC-DWI facilitates excellent visualization of the pituitary region and surrounding normal structures, and its on-console distortion correction technique is convenient. RDC-DWI can clearly depict cavernous sinus invasion of PitNET/pituitary adenoma even without contrast medium. KEY POINTS: • RDC-DWI is an EPI-based DWI technique with a novel on-console distortion correction technique. • RDC-DWI corrects distortion due to B0 field inhomogeneity and eddy current. • We evaluated the usefulness of thin-slice RDC-DWI in non-functioning PitNET/pituitary adenoma. • RDC-DWI exhibited excellent visualization in the pituitary region and surrounding structures. • In addition, the on-console distortion correction of RDC-DWI is clinically convenient.

Evaluating Reproducibility of the ADC and Distortion in Diffusion-weighted Imaging (DWI) with Reverse Encoding Distortion Correction (RDC).

PURPOSE: To compare image distortion and reproducibility of quantitative values between reverse encoding distortion correction (RDC) diffusion-weighted imaging (DWI) and conventional DWI techniques in a phantom study and in healthy volunteers. METHODS: This prospective study was conducted with the approval of our institutional review board. Written informed consent was obtained from each participant. RDC-DWIs were created from images obtained at 3T in three orthogonal directions in a phantom and in 10 participants (mean age, 70.9 years; age range, 63-83 years). Images without distortion correction (noDC-DWI) and those corrected with B0 (B0c-DWI) were also created. To evaluate distortion, coefficients of variation were calculated for each voxel and ROIs were placed at four levels of the brain. To evaluate the reproducibility of apparent diffusion coefficient (ADC) measurements, intra- and inter-scan variability (%CVADC) were calculated from repeated scans of the phantom. Analysis was performed using Wilcoxon signed-rank test with Bonferroni correction, and P < 0.05 was considered statistically significant. RESULTS: In the phantom, distortion was less in RDC-DWI than in B0c-DWI (P < 0.006), and was less in B0c-DWI than in noDC-DWI (P < 0.006). Intra-scan %CVADC was within 1.30%, and inter-scan %CVADC was within 2.99%. In the volunteers, distortion was less in RDC-DWI than in B0c-DWI in three of four locations (P < 0.006), and was less in B0c-DWI than in noDC-DWI (P < 0.006). At the middle cerebellar peduncle, distortion was less in RDC-DWI than in noDC-DWI (P < 0.006), and was less in noDC-DWI than in B0c-DWI (P < 0.0177). CONCLUSION: In both the phantom and in volunteers, distortion was the least in RDC-DWI than in B0c-DWI and noDC-DWI.

Prognostic value of pretreatment FDG PET/CT in uterine cervical cancer according to two major histologic types: squamous cell carcinoma and adenocarcinoma.

Objectives: The aim of this study was to assess the prognostic value of pretreatment Positron emission tomography / computed tomography using 18F-fluorodeoxyglucose (FDG-PET/CT) in cervical cancer according to two major histologic types. Methods: Eighty-three squamous cell carcinoma (SCC) patients and 35 adenocarcinoma (AC) patients who underwent pretreatment FDG-PET/CT were retrospectively analyzed. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were calculated. Kaplan-Meier analyses were used to compare correlations between each PET parameter and overall survival (OS). The prognostic values of imaging and clinical parameters were assessed using uni- and multivariable Cox proportional hazard models. Results: SUVmax, SUVmean, and TLG were significantly higher in SCC than in AC (p<0.01 each). No significant difference in MTV was seen between the two groups (p=0.10). As for Kaplan-Meier analyses, in SCC, patients with SUVmax, SUVmean, MTV, and TLG exceeding cutoff values tended to show worse OS than patients with lower values (p=0.07, p=0.27, p<0.01, and p=0.01, respectively, for OS). On the other hand, in AC, patients with MTV and TLG exceeding cutoff values showed significantly worse PFS and OS (p<0.01 each for OS), while SUVmax and SUVmean were unrelated to OS (p=0.91 and p=0.83, respectively for OS). As for multivariable analyses, in SCC, TLG was identified as an independent prognostic factor for OS (p=0.01). In AC, MTV was identified as an independent prognostic factor for OS (p=0.02). Conclusion: Our preliminary data suggest that FDG-PET/CT would be useful for predicting prognosis in cervical cancer, although the clinical significance of quantitative values may differ according to histopathological type.

Denoising approach with deep learning-based reconstruction for neuromelanin-sensitive MRI: image quality and diagnostic performance.

PURPOSE: Neuromelanin-sensitive MRI (NM-MRI) has proven useful for diagnosing Parkinson's disease (PD) by showing reduced signals in the substantia nigra (SN) and locus coeruleus (LC), but requires a long scan time. The aim of this study was to assess the image quality and diagnostic performance of NM-MRI with a shortened scan time using a denoising approach with deep learning-based reconstruction (dDLR). MATERIALS AND METHODS: We enrolled 22 healthy volunteers, 22 non-PD patients and 22 patients with PD who underwent NM-MRI, and performed manual ROI-based analysis. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in ten healthy volunteers were compared among images with a number of excitations (NEX) of 1 (NEX1), NEX1 images with dDLR (NEX1 + dDLR) and 5-NEX images (NEX5). Acquisition times for NEX1 and NEX5 were 3 min 12 s and 15 min 58 s, respectively. Diagnostic performances using the contrast ratio (CR) of the SN (CR_SN) and LC (CR_LC) and those by visual assessment for differentiating PD from non-PD were also compared between NEX1 and NEX1 + dDLR. RESULTS: Image quality analyses revealed that SNRs and CNRs of the SN and LC in NEX1 + dDLR were significantly higher than in NEX1, and comparable to those in NEX5. In diagnostic performance analysis, areas under the receiver operating characteristic curve (AUC) using CR_SN and CR_LC of NEX1 + dDLR were 0.87 and 0.75, respectively, which had no significant difference with those of NEX1. Visual assessment showed improvement of diagnostic performance by applying dDLR. CONCLUSION: Image quality for NEX1 + dDLR was comparable to that of NEX5. dDLR has the potential to reduce scan time of NM-MRI without degrading image quality. Both 1-NEX NM-MRI with and without dDLR showed high AUCs for diagnosing PD by CR. The results of visual assessment suggest advantages of dDLR. Further tuning of dDLR would be expected to provide clinical merits in diagnosing PD.

FDG-PET findings associated with various medical procedures and treatments.

[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a well-established modality with high sensitivity for the diagnosis and staging of oncologic patients. FDG is taken up by the glucose transporter of the cell membrane and becomes trapped within the cell. In addition to malignant neoplasms, active inflammatory lesions and some kinds of benign tumors also accumulate FDG. Moreover, the degree of uptake into normal organs and tissues depends on various physiological conditions, which is affected by various medical procedures, treatments, and drugs. To avoid misleading interpretations, it is important to recognize possible situations of unexpected abnormal accumulation that mimic tumor lesions. In this review, we present various FDG findings associated with surgical or medical procedures and treatments. Some findings reflect the expected physiological reaction to treatment, and some show inflammation due to prior procedures. Occasionally, FDG-PET visualizes other disorders that are unrelated to the malignancy, which may be associated with the adverse effects of certain drugs that the patient is taking. Careful review of medical records and detailed interviews of patients are thus necessary.

Super-resolution application of generative adversarial network on brain time-of-flight MR angiography: image quality and diagnostic utility evaluation.

OBJECTIVES: To develop a generative adversarial network (GAN) model to improve image resolution of brain time-of-flight MR angiography (TOF-MRA) and to evaluate the image quality and diagnostic utility of the reconstructed images. METHODS: We included 180 patients who underwent 1-min low-resolution (LR) and 4-min high-resolution (routine) brain TOF-MRA scans. We used 50 patients' datasets for training, 12 for quantitative image quality evaluation, and the rest for diagnostic validation. We modified a pix2pix GAN to suit TOF-MRA datasets and fine-tuned GAN-related parameters, including loss functions. Maximum intensity projection images were generated and compared using multi-scale structural similarity (MS-SSIM) and information theoretic-based statistic similarity measure (ISSM) index. Two radiologists scored vessels' visibilities using a 5-point Likert scale. Finally, we evaluated sensitivities and specificities of GAN-MRA in depicting aneurysms, stenoses, and occlusions. RESULTS: The optimal model was achieved with a lambda of 1e5 and L1 + MS-SSIM loss. Image quality metrics for GAN-MRA were higher than those for LR-MRA (MS-SSIM, 0.87 vs. 0.73; ISSM, 0.60 vs. 0.35; p.adjusted < 0.001). Vessels' visibility of GAN-MRA was superior to LR-MRA (rater A, 4.18 vs. 2.53; rater B, 4.61 vs. 2.65; p.adjusted < 0.001). In depicting vascular abnormalities, GAN-MRA showed comparable sensitivities and specificities, with greater sensitivity for aneurysm detection by one rater (93% vs. 84%, p < 0.05). CONCLUSIONS: An optimized GAN could significantly improve the image quality and vessel visibility of low-resolution brain TOF-MRA with equivalent sensitivity and specificity in detecting aneurysms, stenoses, and occlusions. KEY POINTS: • GAN could significantly improve the image quality and vessel visualization of low-resolution brain MR angiography (MRA). • With optimally adjusted training parameters, the GAN model did not degrade diagnostic performance by generating substantial false positives or false negatives. • GAN could be a promising approach for obtaining higher resolution TOF-MRA from images scanned in a fraction of time.

Diagnostic advantage of thin slice 2D MRI and multiplanar reconstruction of the knee joint using deep learning based denoising approach.

The purpose of this study is to evaluate whether thin-slice high-resolution 2D fat-suppressed proton density-weighted image of the knee joint using denoising approach with deep learning-based reconstruction (dDLR) with MPR is more useful than 3D FS-PD multi planar voxel image. Twelve patients who underwent MRI of the knee at 3T and 13 knees were enrolled. Denoising effect was quantitatively evaluated by comparing the coefficient of variation (CV) before and after dDLR. For the qualitative assessment, two radiologists evaluated image quality, artifacts, anatomical structures, and abnormal findings using a 5-point Likert scale between 2D and 3D. All of them were statistically analyzed. Gwet's agreement coefficients were also calculated. For the scores of abnormal findings, we calculated the percentages of the cases with agreement with high confidence. The CV after dDLR was significantly lower than the one before dDLR (p < 0.05). As for image quality, artifacts and anatomical structure, no significant differences were found except for flow artifact (p < 0.05). The agreement was significantly higher in 2D than in 3D in abnormal findings (p < 0.05). In abnormal findings, the percentage with high confidence was higher in 2D than in 3D (p < 0.05). By applying dDLR to 2D, almost equivalent image quality to 3D could be obtained. Furthermore, abnormal findings could be depicted with greater confidence and consistency, indicating that 2D with dDLR can be a promising imaging method for the knee joint disease evaluation.

Detection efficacy of PET/CT with 18F-FSU-880 in patients with suspected recurrent prostate cancer: a prospective single-center study.

PURPOSE: Our objective was to investigate the efficacy of PET/CT with a novel prostate-specific membrane antigen (PSMA)-targeted PET probe, 18F-FSU-880, for detection and localization of recurrent disease in prostate cancer patients in whom recurrence was suspected based on an increase in plasma prostate-specific antigen (PSA) levels after initial treatment. METHODS: This study was a prospective institutional review board-approved study of 72 patients (age 56-84 years, PSA level 0.22-40.00 ng/ml) with suspected relapse of prostate cancer after primary therapy, including radical prostatectomy (RP) (n = 35) or radiation therapy (RT) (n = 37). Patients underwent PET/CT approximately 1 h and 3 h after injection of 18F-FSU-880 (101.8-380 MBq). The correlation between patient-based detection rate and Gleason score (GS) of the primary tumor and plasma PSA levels at the time of PET/CT was evaluated. Maximum standardized uptake values (SUVmax) of the positive uptakes at 1 h post-injection were compared with those at 3 h post-injection. RESULTS: In total, 51 patients (71%) showed at least one positive PSMA PET result. The PSA-stratified detection rates were 22% (2/9), 36% (4/11), 89% (16/18) and 85% (29/34) for PSA levels of 0.2 to < 0.5, 0.5 to < 1.0, 1.0 to < 2.0 and ≥ 2.0 ng/ml, respectively. The GS-stratified detection rates were 33% (2/6), 67% (16/24), 70% (16/23) and 89% (17/19) for GS 6, 7, 8 and 9, respectively. In lesion-based analysis, 157 positive lesions were detected at 3 h post-injection, 18 in the prostate or prostate bed, 65 in lymph nodes, 71 in the bone and 3 in the lung. Two local recurrences, eight pelvic lymph nodes and one distant lymph node were depicted only at 3 h post-injection. SUV max at 3 h post-injection was significantly higher than SUVmax at 1 h post-injection (p < 0.001). CONCLUSION: Our preliminary data suggest that 18F-FSU-880 might be a promising new PSMA-targeting tracer for detecting recurrence after initial treatment in patients with prostate cancer.

Development of a novel Indium-111 radiolabeled mogamulizumab targeting CCR4 for imaging adult T-cell leukemia/lymphoma in vivo.

OBJECTIVE: Adult T-cell leukemia/lymphoma (ATL), caused by human T-cell lymphotropic virus type I (HTLV-1) infection, is among the most aggressive categories and has the worst prognosis among T-cell lymphomas. Mogamulizumab, an anti-CC chemokine receptor 4 (CCR 4), has been shown to be effective in the treatment of ATL; however, some ATL cases are often resistant, particularly the lymphoma-type ATL. To evaluate drug delivery in vivo and identify the distribution of CCR4-positive cells in the body, we developed a novel mogamulizumab tracer labeled with Indium-111 (111In) via diethylenetriaminepentaacetic acid (DTPA) for single-photon emission computerized tomography (SPECT), named [111In]In-DTPA-mogamulizumab, and evaluated its potential for visualizing CCR4 expression in vivo. METHODS: [111In]In-DTPA-mogamulizumab was added to HCT116/CCR4 or HCT116/empty vector (EV) cells, and their radioactivity was measured 1 h after administration. A blocking study was additionally performed by treating HCT116/CCR4 cells with excess mogamulizumab in addition to [111In]In-DTPA-mogamulizumab. The biodistribution and SPECT imaging of [111In]In-DTPA-mogamulizumab in HCT116/CCR4 and HCT116/EV dual-xenografted BALB/c-nu mice were evaluated for 72 h after intravenous injection. RESULTS: [111In]In-DTPA-mogamulizumab was acquired with a radiochemical purity > 95%. The cellular uptake level of [111In]In-DTPA-mogamulizumab by HCT116/CCR4 cells was significantly higher than that by HCT116/EV cells (HCT116/CCR4: 0.951 ± 0.069, HCT116/EV: 0.006 ± 0.001%dose/mg protein, p < 0.01), and the uptake was significantly suppressed by co-incubation with excess mogamulizumab (0.013 ± 0.003%dose/mg protein, p < 0.01). In the in vivo study, the radioactivity of the HCT116/CCR4 tumor tissue was significantly higher than that of the HCT116/EV tumor tissue at 72 h after the administration of [111In]In-DTPA-mogamulizumab (HCT116/CCR4: 20.5 ± 5.4, HCT116/EV: 5.7 ± 1.0%ID/g), and HCT116/CCR4 tumors were clearly and specifically visualized on SPECT imaging. CONCLUSIONS: We have successfully developed a novel SPECT imaging tracer targeting CCR4, [111In]In-DTPA-mogamulizumab, which showed good specificity and pharmacokinetics, indicating potential in visualizing CCR4 expression in vivo.

First-in-Human Evaluation of Positron Emission Tomography/Computed Tomography With [18F]FB(ePEG12)12-Exendin-4: A Phase 1 Clinical Study Targeting GLP-1 Receptor Expression Cells in Pancreas.

Pancreatic ß-cell mass (BCM) has a central importance in the pathophysiology of diabetes mellitus. Recently, pancreatic ß-cell-specific imaging, especially positron emission tomography (PET) with exendin-based probes, has emerged for non-invasive evaluation of BCM. We developed a novel exendin-based probe labeled with fluorine-18, [18F]FB(ePEG12)12-exendin-4 (18F-Ex4) for PET imaging. We subsequently conducted a first-in-human phase 1 study of 18F-Ex4 PET/computed tomography (CT) and investigated the safety and utility for visualizing the pancreas. Six healthy male subjects were enrolled in this study. A low dose (37.0 MBq) of 18F-Ex4 PET/CT was administered (first cohort: n = 2), and subsequently a higher dose (74.0 MBq) was administered (second cohort: n = 4). In the first and second cohorts, 38.6 ± 4.8 and 71.1 ± 4.8 MBq of 18F-Ex4 were administered, respectively. No serious adverse events were observed in both groups. Only one participant in the first cohort showed transient hypoglycemia during the PET scans. 18F-Ex4 PET/CT successfully visualized the pancreas in all participants. The mean standardized uptake value of the pancreas was found to be higher than that in the surrounding organs, except for the bladder and kidney, during the observation. Dosimetry analyses revealed the effective systemic doses of 18F-Ex4 as 0.0164 ± 0.0019 mSv/MBq (first cohort) and 0.0173 ± 0.0020 mSv/MBq (second cohort). 18F-Ex4 PET/CT demonstrated the safety and utility for non-invasive visualization of the pancreas in healthy male subjects. 18F-Ex4 is promising for clinical PET imaging targeting pancreatic ß cells.

Physiologically decreased F-18 fluorodeoxyglucose uptake in the lower vertebrae associated with daily drinking habit in Japanese men with alcohol flushing reaction.

Alcohol flushing reaction (AFR) is known as one of the risks for esophageal squamous cell cancer, and scientists have been elucidating this issue. However, little attention has been given to relevant imaging features. This study aims to investigate whether physiological 18F-fluorodeoxyglucose (FDG) uptake patterns in vertebrae are associated with drinking habits or AFR. Japanese male patients who underwent FDG positron emission computed tomography for evaluation of their known or suspected malignancies or inflammatory diseases were asked about their drinking habits and AFR. Altogether, 192 patients, 139 every-day drinkers and 53 non-drinkers were evaluated. Comparing the FDG uptake between that in the thoracic region and that in the lumbar region, vertebral uptake was visually classified into four patterns: Ld, dominant in lumbar region; TL, almost equal in both regions; BL, slightly higher in thoracic region (borderline pattern); Td, dominant in thoracic region. The uptake patterns were evaluated according to drinking habit (every-day drinker or non-drinker), AFR (flusher or non-flusher), and the combination of these two factors (habit/reaction: every-day drinker/flusher, every-day drinker/non-flusher, non-drinker/flusher, or non-drinker/non-flusher). There were 95 flushers (51 every-day drinkers and 44 non-drinkers) and 97 non-flushers (88 every-day drinkers and 9 non-drinkers). Ld, TL, BL, and Td patterns were observed in 0, 109 (56.8%), 31 (16.1%), and 52 (27.1%) patients, respectively. Td and BL patterns were more frequently observed in every-day drinkers compared with non-drinkers (p = 0.0467). Though the uptake patterns did not differ between flushers and non-flushers (p = 0.116), the Td pattern was more frequently observed in every-day drinkers/flushers (51%) compared with every-day drinkers/non-flushers (20.5%), non-drinkers/flushers (13.6%), and non-drinkers/non-flushers (22.2%) (p = 0.0014). The Td pattern was observed in patients with various diseases, with higher frequency in esophageal cancer, head and neck cancer, and lung cancer compared with other diseases. In conclusion, drinking habits and AFR were related to the vertebral uptake pattern with decreased uptake in the lumbar region in Japanese male patients.

Diagnostic performance of 68Ga-DOTATOC PET/CT in tumor-induced osteomalacia.

OBJECTIVE: Tumor-induced osteomalacia (TIO) is caused by typically small tumors that secrete fibroblast growth factor 23 (FGF23). As tumor resection is the only effective treatment for TIO, it is important to detect the culprit tumor. We aimed to assess the utility of 68Gallium-DOTA-D-Phe(1)-Tyr(3)-octreotide (68Ga-DOTATOC) PET/CT in TIO and the correlation between biochemical parameters and the PET/CT results. METHODS: Thirty-five patients with clinically suspected TIO who had undergone 68Ga-DOTATOC PET/CT were retrospectively analyzed. 68Ga-DOTATOC PET/CT results were compared with biochemical parameters and the final diagnosis, including histopathology. RESULTS: 68Ga-DOTATOC PET/CT detected focal uptake consistent with TIO in 21/35 patients, one of which was considered false positive. In 16 patients, the cause of osteomalacia was confirmed histologically as phosphaturic mesenchymal tumor (n = 15) or fibrous dysplasia (n = 1). The other four patients were judged clinically as true positive by subsequent MRI and the clinical course. Overall, the detection rate of 68Ga-DOTATOC PET/CT was 57% (20/35). Median tumor maximum standardized uptake value (SUVmax) was 6.9 (range 1.5-37.7). There was no significant difference in serum intact FGF23 level between DOTATOC-positive and DOTATOC-negative cases, and no significant correlation was observed between intact FGF23 level and tumor SUVmax. CONCLUSIONS: 68Ga-DOTATOC PET/CT was clinically useful in detecting culprit tumors and subsequent patient management in TIO.

Clinical value of PET/CT with carbon-11 4DST in the evaluation of malignant and benign lung tumors.

OBJECTIVES: The aim of this study was to assess the clinical value of [11C]4DST uptake in patients with lung nodules, including benign and malignant tumors, and to assess the correlation between [11C]4DST uptake and proliferative activity of tumors in comparison with [18F]FDG uptake. METHODS: Twenty-six patients (22 males and 4 females, mean age of 65.5-year-old) were analyzed in this prospective study. Patients underwent [11C]4DST and [18F]FDG PET/CT imaging on the same day. Diagnosis of each lung nodule was confirmed by histopathological examination of tissue specimens at surgery, or during clinical follow-up after the PET/CT studies. To assess the utility of the semi-quantitative evaluation method, the SUVmax was calculated of [11C]4DST and [18F]FDG uptake by the lesion. Proliferative activities of each tumor as indicated by the immunohistochemical Ki-67 index was also estimated using surgical specimens of patients. Then the relationship between the SUVmax of both PET/CT and the Ki-67 index was examined. Furthermore, the relationship between the uptake of [11C]4DST or [18F]FDG and the histopathological findings, the clinical stage, and the clinical outcome of patients were also assessed. RESULTS: There was a positive linear relationship between the SUVmax of [11C]4DST images and the Ki-67 index (Correlation coefficients = 0.68). The SUVmax of [11C]4DST in the 26 lung nodules were 1.65 ± 0.40 for benign lesions, 3.09 ± 0.83 for adenocarcinomas (P < 0.001 between benign and adenocarcinoma), and 2.92 ± 0.58 for SqCCs (P < 0.001 between benign and SqCC). Whereas, the SUVmax of [18F]FDG were 2.38 ± 2.27 for benign lesions, 6.63 ± 4.24 for adenocarcinomas (n.s.), and 7.52 ± 2.84 for SqCCs (n.s.). The relationship between TNM tumor stage and the SUVmax of [11C]4DST were 2.54 ± 0.37 for T1, 3.48 ± 0.57 for T2, and 4.17 ± 0.72 for T3 (P < 0.005 between T1 and T2, and P < 0.001 between T1 and T3). In comparison with the TNM pathological stage, SUVmax of [11C]4DST were 2.63 ± 0.49 for stage I, 3.36 ± 0.23 for stage II, 3.40 ± 1.12 for stage III, and 4.65 for stage IV (P < 0.05 between stages I and II). In comparison of the clinical outcome, the SUVmax of [11C]4DST were 2.72 ± 0.56 for the no recurrence (No Rec.) group, 3.10 ± 0.33 for the recurrence-free with adjuvant chemotherapy after the surgery (the No Rec. Adjv. CTx. group) and 4.66 ± 0.02 for the recurrence group (Rec. group) (P < 0.001 between the No Rec and Rec. groups, and P < 0.005 between the No Rec. Adjv. CTx. and Rec. groups). CONCLUSIONS: PET/CT with [11C]4DST is as feasible for imaging of lung tumors as [18F]FDG PET/CT. For diagnosing lung tumors, [11C]4DST PET is useful in distinguishing benign nodules from malignancies. [11C]4DST uptake in lung carcinomas is correlated with the proliferative activity of tumors, indicating a promising noninvasive PET imaging of DNA synthesis in malignant lung tumors.

Increased [18F]FMISO accumulation under hypoxia by multidrug-resistant protein 1 inhibitors.

BACKGROUND: [18F]Fluoromisonidazole ([18F]FMISO) is a PET imaging probe widely used for the detection of hypoxia. We previously reported that [18F]FMISO is metabolized to the glutathione conjugate of the reduced form in hypoxic cells. In addition, we found that the [18F]FMISO uptake level varied depending on the cellular glutathione conjugation and excretion ability such as enzyme activity of glutathione-S-transferase and expression levels of multidrug resistance-associated protein 1 (MRP1, an efflux transporter), in addition to the cellular hypoxic state. In this study, we evaluated whether MRP1 activity affected [18F]FMISO PET imaging. METHODS: FaDu human pharyngeal squamous cell carcinoma cells were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, incubated with [18F]FMISO for 4 h under hypoxia, and their radioactivity was then measured. FaDu tumor-bearing mice were intravenously injected with [18F]FMISO, and PET/CT images were acquired at 4 h post-injection (1st PET scan). Two days later, the same mice were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, and PET/CT images were acquired (2nd PET scan). RESULTS: FaDu cells pretreated with MRP1 inhibitors exhibited significantly higher radioactivity than those without inhibitor treatment (cyclosporine A: 6.91 ± 0.27, lapatinib: 10.03 ± 0.47, MK-571: 10.15 ± 0.44%dose/mg protein, p < 0.01). In the in vivo PET study, the SUVmean ratio in tumors [calculated as after treatment (2nd PET scan)/before treatment of MRP1 inhibitors (1st PET scan)] of the mice treated with MRP1 inhibitors was significantly higher than those of control mice (cyclosporine A: 2.6 ± 0.7, lapatinib: 2.2 ± 0.7, MK-571: 2.2 ± 0.7, control: 1.2 ± 0.2, p < 0.05). CONCLUSION: In this study, we revealed that MRP1 inhibitors increase [18F]FMISO accumulation in hypoxic cells. This suggests that [18F]FMISO-PET imaging is affected by MRP1 inhibitors independent of the hypoxic state.

Deep Learning-based Noise Reduction for Fast Volume Diffusion Tensor Imaging: Assessing the Noise Reduction Effect and Reliability of Diffusion Metrics.

To assess the feasibility of a denoising approach with deep learning-based reconstruction (dDLR) for fast volume simultaneous multi-slice diffusion tensor imaging of the brain, noise reduction effects and the reliability of diffusion metrics were evaluated with 20 patients. Image noise was significantly decreased with dDLR. Although fractional anisotropy (FA) of deep gray matter was overestimated when the number of image acquisitions was one (NAQ1), FA in NAQ1 with dDLR became closer to that in NAQ5.

Qualitative and Quantitative Assessment of Nonlocal Means Reconstruction Algorithm in a Flexible PET Scanner.

OBJECTIVE. Flexible PET (fxPET) was designed to fit existing MRI systems. The newly modified nonlocal means (NLM) algorithm is combined with the 3D dynamic row-action maximum likelihood algorithm (DRAMA). We investigated qualitative and quantitative acceptability of fxPET images reconstructed by modified NLM compared with whole-body (WB) PET/CT images and conventional 3D DRAMA reconstruction alone. MATERIALS AND METHODS. Fifty-nine patients with known or suspected malignancies underwent WB PET/CT scanning approximately 1 hour after the injection of 18F-FDG, after which they underwent fxPET scanning. Two readers rated the quality of fxPET images by consensus. Detection rate (the proportion of lesions found on PET), maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), tumor-to-normal liver ratio (TNR), and background liver signal-to-noise ratio (SNR) were compared among the three datasets. RESULTS. Higher image quality was obtained by modified NLM reconstruction than by conventional reconstruction without statistical significance. The detection rate was comparable among three datasets. SUVmax was significantly higher, and MTV and TLG were significantly lower in the modified NLM dataset (p < 0.002) than in the other two datasets, with significantly positive correlations (p < 0.001; Spearman rank correlation coefficient, 0.87-0.99). The TNRs in modified NLM images were significantly larger than in the other datasets (p < 0.05). The background SNRs in modified NLM images were comparable with those in WB PET/CT images, and significantly higher than in the conventional fxPET images (p < 0.005). CONCLUSION. The modified NLM algorithm was clinically acceptable, yielding higher TNR and background SNR compared with conventional reconstruction. Image quality and the lesion detection rate were comparable in this population.

Radiolabeled Human Monoclonal Antibody 067-213 has the Potential for Noninvasive Quantification of CD73 Expression.

BACKGROUND: CD73 is an ectonucleotidase regulating extracellular adenosine concentration and plays an important role in adenosine-mediated immunosuppressive pathways. The efficacy of CD73-targeted therapy depends on the expression levels of CD73; therefore, monitoring CD73 status in cancer patients would provide helpful information for selection of patients who would benefit from CD73-targeted therapy. Here, we evaluated the ability of 111In-labeled antibody 067-213, which has high affinity for human CD73, to act as a noninvasive imaging probe. METHODS: Cell binding and competitive inhibition assays for 111In-labeled 067-213 were conducted using MIAPaCa-2 (high CD73 expression) and A431 (low CD73 expression) cells. For in vivo assessments, biodistribution and SPECT/CT studies were conducted in MIAPaCa-2 and A431 tumor-bearing mice. To estimate the absorbed dose in humans, biodistribution and SPECT/CT studies were conducted in healthy rats. RESULTS: 111In-labeled 067-213 bound to MIAPaCa-2 and A431 cells in a CD73-dependent manner and the affinity loss after 111In-labeling was limited. Biodistribution and SPECT/CT studies with 111In-labeled 067-213 in mice showed high uptake in MIAPaCa-2 tumors and lower uptake in A431 tumors. In rats, the probe did not show high uptake in normal organs, including endogenously CD73-expressing organs. The estimated absorbed doses in humans were reasonably low. CONCLUSIONS: 111In-labeled 067-213 showed CD73-expression-dependent tumor uptake and low uptake in normal organs and tissues. Radiolabeled 067-213 holds promise as an imaging probe for noninvasive evaluation of CD73 expression levels in patients. Our data encourage further clinical studies to clarify a role for CD73 monitoring in patients receiving CD73-targeted immune therapy.

Prognostic Value of Quantitative Parameters of 18F-FDG PET/CT for Patients With Angiosarcoma.

OBJECTIVE. The purpose of this study was to evaluate quantitative parameters in 18F-FDG PET/CT in terms of correlation with histologic grade and overall survival in patients with angiosarcoma. MATERIALS AND METHODS. The cases of 16 patients with histologically confirmed angiosarcoma who had undergone pretreatment FDG PET/CT were retrospectively analyzed. Maximum standardized uptake value for the primary tumor (pSUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) for the whole body, tumor-to-blood ratio (TBR) for the primary tumor, and summed ratios of tumor-to-blood glycolytic activity for all lesions (whole-body TLG ratio) were calculated. Tumors were divided into high grade and low grade, according to the pathologic results. Correlations between these metabolic parameters and tumor grade were investigated. The prognostic value of these parameters and various clinicopathologic factors with respect to overall survival was assessed with the Cox proportional hazards regression model. RESULTS. Histopathologic examination revealed 10 high-grade and six low-grade tumors. Among the quantitative parameters, pSUVmax (p < 0.0001) and primary TBR (p = 0.0003) were significantly higher for high-grade tumors than for low-grade tumors. Ten patients died during follow-up (median survival time, 19.6 months). Higher pSUVmax (p = 0.040), MTV (p = 0.016), whole-body TLG (p = 0.010), primary TBR (p = 0.019), and whole-body TLG ratio (p = 0.007) correlated significantly with poorer overall survival. Single lesion at initial diagnosis (p = 0.0008) and performance of curative surgery (p = 0.0008) were strong favorable prognostic factors for overall survival, but histologic grade was not identified as a significant predictor. CONCLUSION. In angiosarcoma, high-grade tumors had significantly higher pSUVmax and primary TBR at FDG PET/CT. All quantitative parameters evaluated in this study were found to be significant prognostic factors for overall survival.