Lost in space(s): Multimodal neuroimaging of disorientation along the Alzheimer's disease continuum.

Orientation is a fundamental cognitive faculty and the bedrock of the neurologic examination. Orientation is defined as the alignment between an individual's internal representation and the external world in the spatial, temporal, and social domains. While spatial disorientation is a recognized hallmark of Alzheimer's disease (AD), little is known about disorientation beyond space in AD. This study aimed to explore disorientation in spatial, temporal, and social domains along the AD continuum. Fifty-one participants along the AD continuum performed an ecological orientation task in the spatial, temporal, and social domains while undergoing functional MRI. Disorientation in AD followed a three-way association between orientation domain, brain region, and disease stage. Specifically, patients with early amnestic mild cognitive impairment exhibited spatio-temporal disorientation and reduced brain activity in temporoparietal regions, while patients with AD dementia showed additional social disorientation and reduced brain activity in frontoparietal regions. Furthermore, patterns of hypoactivation overlapped different subnetworks of the default mode network, patterns of fluorodeoxyglucose hypometabolism, and cortical atrophy characteristic of AD. Our results suggest that AD may encompass a disorder of orientation, characterized by a biphasic process manifesting as early spatio-temporal and late social disorientation. As such, disorientation may offer a unique window into the clinicopathological progression of AD. SIGNIFICANCE STATEMENT: Despite extensive research into Alzheimer's disease (AD), its core cognitive deficit remains a matter of debate. In this study, we investigated whether orientation, defined as the ability to align internal representations with the external world in spatial, temporal, and social domains, constitutes a core cognitive deficit in AD. To do so, we used PET-fMRI imaging to collect behavioral, functional, and metabolic data from 51 participants along the AD continuum. Our findings suggest that AD may constitute a disorder of orientation, characterized by an early spatio-temporal disorientation and followed by late social disorientation, manifesting in task-evoked and neurodegenerative changes. We propose that a profile of disorientation across multiple domains offers a unique window into the progression of AD and as such could greatly benefit disease diagnosis, monitoring, and evaluation of treatment response.

Mutant PIK3CA is a targetable driver alteration in histiocytic neoplasms.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterized by the accumulation of clonal mononuclear phagocyte system cells expressing CD1a and CD207. In the past decade, molecular profiling of LCH as well as other histiocytic neoplasms demonstrated that these diseases are driven by MAPK activating alterations, with somatic BRAFV600E mutations in >50% of patients with LCH, and clinical inhibition of MAPK signaling has demonstrated remarkable clinical efficacy. At the same time, activating alterations in kinase-encoding genes, such as PIK3CA, ALK, RET, and CSF1R, which can activate mitogenic pathways independent from the MAPK pathway, have been reported in a subset of histiocytic neoplasms with anecdotal evidence of successful targeted treatment of histiocytoses harboring driver alterations in RET, ALK, and CSF1R. However, evidence supporting the biological consequences of expression of PIK3CA mutations in hematopoietic cells has been lacking, and whether targeted inhibition of PI3K is clinically efficacious in histiocytic neoplasms is unknown. Here, we provide evidence that activating mutations in PIK3CA can drive histiocytic neoplasms in vivo using a conditional knockin mouse expressing mutant PIK3CAH1047R in monocyte/dendritic cell progenitors. In parallel, we demonstrate successful treatment of PIK3CA-mutated, multisystemic LCH using alpelisib, an inhibitor of the alpha catalytic subunit of PI3K. Alpelisib demonstrated a tolerable safety profile at a dose of 750 mg per week and clinical and metabolic complete remission in a patient with PIK3CA-mutated LCH. These data demonstrate PIK3CA as a targetable noncanonical driver of LCH and underscore the importance of mutational analysis-based personalized treatment in histiocytic neoplasms.

Lost in space(s): multimodal neuroimaging of disorientation along the Alzheimer's disease continuum.

Orientation is a fundamental cognitive faculty, allowing the behaving self to link his/her current state to their internal representations of the external world. Once exclusively linked to knowledge of the current place and present time, in recent years, the concept of orientation has evolved to include processing of social, temporal, and abstract relations. Concordantly with the growing focus on orientation, spatial disorientation has been increasingly recognized as a hallmark symptom of Alzheimer's disease (AD). However, few studies have sought to explore disorientation along the AD continuum beyond the spatial domain. 51 participants along the AD continuum performed an orientation task in the spatial, temporal and social domains. Under functional magnetic resonance imaging (fMRI), participants determined which of two familiar places/events/people is geographically/ chronologically/ socially closer to them, respectively. A series of analyses revealed disorientation along the AD- continuum to follow a three-way association between (1) orientation domain, (2) brain region, and (3) disease stage. Specifically, participants with MCI exhibited impaired spatio-temporal orientation and reduced task-evoked activity in temporoparietal regions, while participants with AD dementia exhibited impaired social orientation and reduced task-evoked activity in frontoparietal regions. Furthermore, these patterns of hypoactivation coincided with Default Mode Network (DMN) sub-networks, with spatio-temporal orientation activation overlapping DMN-C and social orientation with DMN-A. Finally, these patterns of disorientation- associated hypoactivations coincided with patterns of fluorodeoxyglucose (FDG) hypometabolism and cortical atrophy characteristic to AD-dementia. Taken together, our results suggest that AD may constitute a disorder of orientation, characterized by a biphasic process as (1) early spatio-temporal and (2) late social disorientation, concurrently manifesting in task-evoked and neurodegenerative changes in temporoparietal and parieto-frontal brain networks, respectively. We propose that a profile of disorientation across multiple domains offers a unique window into the progression of AD.

Simultaneous multislice diffusion-weighted imaging versus standard diffusion-weighted imaging in whole-body PET/MRI.

OBJECTIVE: To compare standard (STD-DWI) single-shot echo-planar imaging DWI and simultaneous multislice (SMS) DWI during whole-body positron emission tomography (PET)/MRI regarding acquisition time, image quality, and lesion detection. METHODS: Eighty-three adults (47 females, 57%), median age of 64 years (IQR 52-71), were prospectively enrolled from August 2018 to March 2020. Inclusion criteria were (a) abdominal or pelvic tumors and (b) PET/MRI referral from a clinician. Patients were excluded if whole-body acquisition of STD-DWI and SMS-DWI sequences was not completed. The evaluated sequences were axial STD-DWI at b-values 50-400-800 s/mm2 and the apparent diffusion coefficient (ADC), and axial SMS-DWI at b-values 50-300-800 s/mm2 and ADC, acquired with a 3-T PET/MRI scanner. Three radiologists rated each sequence's quality on a five-point scale. Lesion detection was quantified using the anatomic MRI sequences and PET as the reference standard. Regression models were constructed to quantify the association between all imaging outcomes/scores and sequence type. RESULTS: The median whole-body STD-DWI acquisition time was 14.8 min (IQR 14.1-16.0) versus 7.0 min (IQR 6.7-7.2) for whole-body SMS-DWI, p < 0.001. SMS-DWI image quality scores were higher than STD-DWI in the abdomen (OR 5.31, 95% CI 2.76-10.22, p < 0.001), but lower in the cervicothoracic junction (OR 0.21, 95% CI 0.10-0.43, p < 0.001). There was no significant difference in the chest, mediastinum, pelvis, and rectum. STD-DWI detected 276/352 (78%) lesions while SMS-DWI located 296/352 (84%, OR 1.46, 95% CI 1.02-2.07, p = 0.038). CONCLUSIONS: In cancer staging and restaging, SMS-DWI abbreviates acquisition while maintaining or improving the diagnostic yield in most anatomic regions. KEY POINTS: • Simultaneous multislice diffusion-weighted imaging enables faster whole-body image acquisition. • Simultaneous multislice diffusion-weighted imaging maintains or improves image quality when compared to single-shot echo-planar diffusion-weighted imaging in most anatomical regions. • Simultaneous multislice diffusion-weighted imaging leads to superior lesion detection.

Neoadjuvant 177Lu-PSMA-I&T Radionuclide Treatment in Patients with High-risk Prostate Cancer Before Radical Prostatectomy: A Single-arm Phase 1 Trial.

BACKGROUND: High-risk localized prostate cancer (HRLPC) has a substantial risk of disease progression despite local treatment. Neoadjuvant systemic therapy before definitive local therapy may improve oncological outcomes by targeting the primary tumor and micrometastatic disease. OBJECTIVE: To evaluate whether a lutetium-177 prostate-specific membrane antigen radioligand (LuPSMA) can be safely administered to patients with HRLPC before robot-assisted radical prostatectomy (RARP) and to describe immediate oncological outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was an open-label, single-arm clinical trial. Patients with HRLPC and elevated radioligand uptake on PSMA positron emission tomography/computed tomography were enrolled. Two or three LuPSMA radioligand doses (7.4 GBq) were given at 2-wk intervals. RARP with lymph node dissection was performed 4 wk after the last LuPSMA dose. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The rate of surgical complications, operative parameters, changes in functional and quality-of-life measures, and immediate oncological outcomes (histological findings and biochemical response) were measured. Data were analyzed descriptively. RESULTS AND LIMITATIONS: Fourteen patients participated (median age 67 yr). Prostate-specific antigen decreased by 17% (interquartile range [IQR] 9-50%) after two LuPSMA doses and 34% (IQR 11-60%) after three doses. Thirteen patients underwent RARP with no identifiable anatomical changes or intraoperative complications. Four patients (30%) had postoperative complications (pneumonia, pulmonary embolism, urinary leak with urinary tract infection). At 3 mo postoperatively, 12 patients (92%) required one pad or less. Final whole-mount pathology showed positive surgical margins (PSMs) in seven patients (53%) and downgrading to International Society of Urological Pathology grade group 3 in three patients (23%). Treatment-related effects included a clear vacuolated cytoplasm and pyknotic nuclei. CONCLUSIONS: LuPSMA followed by RARP appears to be surgically safe. While oncological outcomes are pending, continence recovery seems to be unaffected by LuPSMA treatment. PATIENT SUMMARY: We evaluated outcomes for patients with aggressive localized prostate cancer who received treatment with a radioactive agent before surgical removal of their prostate. This approach appears to be safe and feasible, but its therapeutic efficacy is still unknown.

Effect of steroid treatment on the diagnostic yield of baseline 18f-fluorodeoxyglucose positron emission tomography in aggressive B cell lymphoma.

Aggressive B cell lymphoma often requires prompt steroid treatment, even before baseline 18f-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and definitive treatment, to alleviate symptoms or prevent organ damage. Since lymphoma is a steroid-sensitive malignancy, there are concerns that steroids might affect the results of FDG PET/CT and decrease its diagnostic yield. The aim of the current study was to evaluate the effect of steroids administered before baseline PET/CT on the maximum standardized uptake value (SUVmax) and additional PET/CT parameters. Retrospective review of the database in a tertiary medical center yielded 178 patients newly diagnosed with aggressive B cell lymphoma between January 2017 and May 2020 who had an available baseline FDG PET/CT scan. The cohort was divided into patients who received steroids before PET/CT (n = 47) and those who did not (n = 131), and the groups were compared for SUVmax and additional PET/CT parameters. The steroid-treated group had a higher disease stage and lactate dehydrogenase level compared to the steroid-naïve group, with a trend toward a higher international prognostic index. There was no significant between-group difference in SUVmax (P = 0.61). This finding remained consistent across steroid treatment durations and dosage regimens. Further evaluation revealed a significantly larger mean tumor volume and a trend toward a higher tumor metabolic burden in the steroid-treated group, yet no between-group difference in SUV mean or other PET/CT parameters. In this retrospective analysis of patients with aggressive B cell lymphoma, steroid prophase prior to baseline PET/CT did not decrease the diagnostic yield of the scan. However, further studies are required to fully appreciate the impact of steroids on PET CT parameters.

Clinical and pathological predictors for FDG-PET/CT avidity in patients with marginal zone lymphoma-a retrospective cohort study.

BACKGROUND: The clinical value of FDG-PET/CT for staging and monitoring treatment response in patients with aggressive lymphoma is well established. Conversely, its role in the assessment and management of marginal zone lymphoma (MZL) is less conclusive. We aimed to assess clinical, laboratory, and pathological predictors for FDG uptake in these patients, in an attempt to identify MZL patients whose management will benefit from this imaging modality. METHODS: In this single-center, retrospective cohort study, we included all adult patients diagnosed with MZL at the Rabin Medical Center between January 2006 and December 2020 who underwent FDG-PET/CT at the time of diagnosis. Primary outcomes were FDG avidity (defined as a visual assessment of at least moderate intensity), SUVmax, and SUVliver. Variables such as advanced clinical stage, primary disease site, hemoglobin level (Hb), platelet count (Plt), serum albumin, LDH level, ß-2 microglobulin, and Ki 67 index were evaluated univariate and multivariate analysis using logistic and linear regression models. Association between FDG avidity and progression-free and overall survival was evaluated using Kaplan-Meier curves and Cox regression analysis. RESULTS: A total of 207 MZL patients were included in this study, 76 of whom (36.7%) had FDG-avid disease. Baseline patients' characteristics such as age, gender, and comorbid conditions were similar between patients with and without significant FDG uptake. In a multivariate logistic regression model, non-gastric MALT (OR 4.2, 95% CI 1.78-10), Ki 67 index ≥ 15% (OR 3.64, 95% CI 1.36-9.76), and elevated LDH level (OR 8.6, 95% CI 3.2-22.8) were all associated with positive FDG avidity. In a multivariate linear regression model, a combination of advanced clinical stage, specific disease subtypes, LDH level, and Ki 67 index predicted the value of SUVmax (P value < 0.001; adjusted R2 = 33.8%) and SUVmax/SUVliver (P value < 0.001; adjusted R2 = 27%). Baseline FDG avidity was associated to PFS and OS only in univariate analyses. CONCLUSIONS: In this retrospective cohort study, we present prediction models for positive FDG uptake and SUVmax in MZL patients. These models aim to help clinicians choose patients suitable for incorporation of FDG-PET/CT for staging and monitoring disease and reduce the costs of redundant tests.

Early prediction of residual disease after neoadjuvant chemoradiotherapy and cetuximab for locally advanced esophageal cancer using 18F-FDG PET-CT imaging: a prospective cohort study.

Background: Previous studies in locally advanced esophageal cancer (LAEC) suggested that a change in the tumor's metabolic response, i.e., decrease of its interim 18F-FDG uptake compared with baseline, may predict histopathological response. We evaluated the possible predictive correlation between various PET-CT and histopathological parameters following a neoadjuvant biological-containing chemoradiotherapy (CRT) regimen. Methods: Patients with resectable LAEC received neoadjuvant cisplatin/5-fluorouracil-based CRT and cetuximab following one cycle of induction chemotherapy and cetuximab. Changes in maximum and mean standardized uptake values (ΔSUV-max and ΔSUV-mean, respectively) and metabolic tumor volume (ΔMTV), measured by PET-CT at baseline and 2 weeks after the onset of treatment, were compared with histopathological findings at surgery. Histopathological response was defined by tumor regression grade (TRG), pathological complete response (pCR) and microscopic or macroscopic residual disease (RD). Results: Of 18 patients, 13 (72%) with adenocarcinoma (AC) and 5 (28%) with squamous cell carcinoma (SCC), were included. None of the changes in the parameters of PET was associated with pCR; only ΔSUV-mean was associated with TRG in the AC cohort. In contrast, both ΔSUV-mean% and ΔSUV-max% were significantly associated with RD, both in the whole cohort and in the AC cohort. Changes in FDG-uptake predicted RD2 at surgery: only patients with less than 13% decrease in SUV-mean% or less than 29% decrease in SUV-max% had RD2, while all patients with RD0 or RD1 had greater reductions [100% specificity and 100% positive predictive value (PPV)]. Conclusions: Changes in ΔSUV-max and ΔSUV-mean after two weeks of onset of cetuximab-based neoadjuvant chemotherapy for LAEC may predict macroscopic RD but not TRG or pCR at surgery.

PET/MRI and PET/CT Radiomics in Primary Cervical Cancer: A Pilot Study on the Correlation of Pelvic PET, MRI, and CT Derived Image Features.

PURPOSE: To evaluate the correlation of radiomic features in pelvic [2-deoxy-2-18F]fluoro-D-glucose positron emission tomography/magnetic resonance imaging and computed tomography ([18F]FDG PET/MRI and [18F]FDG PET/CT) in patients with primary cervical cancer (CCa). PROCEDURES: Nineteen patients with histologically confirmed primary squamous cell carcinoma of the cervix underwent same-day [18F]FDG PET/MRI and PET/CT. Two nuclear medicine physicians performed a consensus reading in random order. Free-hand regions of interest covering the primary cervical tumors were drawn on PET, contrast-enhanced pelvic CT, and pelvic MR (T2 weighted and ADC) images. Several basic imaging features, standard uptake values (SUVmean, SUVmax, and SUVpeak), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and more advanced texture analysis features were calculated. Pearson's correlation test was used to assess the correlation between each pair of features. Features were compared between local and metastatic tumors, and their role in predicting metastasis was evaluated by receiver operating characteristic curves. RESULTS: For a total of 101 extracted features, 1104/5050 pairs of features showed a significant correlation (ρ ≥ 0.70, p < 0.05). There was a strong correlation between 190/484 PET pairs of features from PET/MRI and PET/CT, 91/418 pairs of CT and PET from PET/CT, 79/418 pairs of T2 and PET from PET/MRI, and 50/418 pairs of ADC and PET from PET/MRI. Significant difference was seen between eight features in local and metastatic tumors including MTV, TLG, and entropy on PET from PET/CT; MTV and TLG on PET from PET/MRI; compactness and entropy on T2; and entropy on ADC images. CONCLUSIONS: We demonstrated strong correlation of many extracted radiomic features between PET/MRI and PET/CT. Eight radiomic features calculated on PET/CT and PET/MRI were significantly different between local and metastatic CCa. This study paves the way for future studies to evaluate the diagnostic and predictive potential of radiomics that could guide clinicians toward personalized patients care.

Diagnostic Performance of 68Ga Prostate-specific Membrane Antigen PET/MRI Compared with Multiparametric MRI for Detecting Clinically Significant Prostate Cancer.

Background Gallium 68 (68Ga) prostate-specific membrane antigen (PSMA) PET/MRI may improve detection of clinically significant prostate cancer (CSPC). Purpose To compare the sensitivity and specificity of 68Ga-PSMA PET/MRI with multiparametric MRI for detecting CSPC. Materials and Methods Men with prostate specific antigen levels of 2.5-20 ng/mL prospectively underwent 68Ga-PSMA PET/MRI, including multiparametric MRI sequences, between June 2019 and March 2020. Imaging was evaluated independently by two radiologists by using the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. Sensitivity and specificity for CSPC (International Society of Urological Pathology grade group ≥ 2) were compared for 68Ga-PSMA PET/MRI and multiparametric MRI by using the McNemar test. Decision curve analysis compared the net benefit of each imaging strategy. Results Ninety-nine men (median age, 67 years; interquartile range, 62-71 years) were included; 79% (78 of 99) underwent biopsy. CSPC was detected in 32% (25 of 78). For CSPC, specificity was higher for 68Ga-PSMA PET/MRI than multiparametric MRI (76% [95% CI: 62, 86] vs 49% [95% CI: 35, 63], respectively; P < .001). Sensitivity was similar (88% [95% CI: 69, 98] vs 92% [95% CI: 74, 99], respectively; P > .99). For PI-RADS 3 lesions, specificity was also higher for 68Ga-PSMA PET/MRI than for multiparametric MRI: 86% (95% CI: 73, 95) versus 59% (95% CI: 43, 74), respectively (P = .002). Decision curve analysis showed that biopsies targeted to PSMA uptake increased the net benefit of multiparametric MRI only among PI-RADS 3 lesions. The net benefit of targeted biopsy for a PI-RADS 3 lesion with PSMA uptake was higher across all threshold probabilities over 8%. The net benefit of targeted biopsy was similar for PI-RADS 4 and 5 lesions, regardless of PSMA uptake. Conclusions Gallium 68 prostate-specific membrane antigen PET/MRI improved specificity for clinically significant prostate cancer compared with multiparametric MRI, particularly in Prostate Imaging Reporting and Data System grade 3 lesions. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Williams and Estes in this issue.

Clinical impact of PET/MRI in oligometastatic colorectal cancer.

BACKGROUND: Oligometastatic colorectal cancer (CRC) is potentially curable and demands individualised strategies. METHODS: This single-centre retrospective study investigated if positron emission tomography (PET)/magnetic resonance imaging (MR) had a clinical impact on oligometastatic CRC relative to the standard of care imaging (SCI). Adult patients with oligometastatic CRC on SCI who also underwent PET/MR between 3/2016 and 3/2019 were included. The exclusion criterion was lack of confirmatory standard of reference, either surgical pathology, intraoperative gross confirmation or imaging follow-up. SCI consisted of contrast-enhanced (CE) computed tomography (CT) of the chest/abdomen/pelvis, abdominal/pelvic CE-MR, and/or CE whole-body PET/CT with diagnostic quality (i.e. standard radiation dose) CT. Follow-up was evaluated until 3/2020. RESULTS: Thirty-one patients constituted the cohort, 16 (52%) male, median patient age was 53 years (interquartile range: 49-65 years). PET/MR and SCI results were divergent in 19% (95% CI 9-37%) of the cases, with PET/MR leading to management changes in all of them. The diagnostic accuracy of PET/MR was 90 ± 5%, versus 71 ± 8% for SCI. In a pairwise analysis, PET/MR outperformed SCI when compared to the reference standard (p = 0.0412). CONCLUSIONS: These findings suggest the potential usefulness of PET/MR in the management of oligometastatic CRC.

The Pattern of Use of PET/CT Scans in the Clinical Management of Chronic Lymphocytic Leukemia.

BACKGROUND: The study aimed to evaluate the utilization patterns of positron emission tomography/computed tomography (PET/CT) in chronic lymphocytic leukemia (CLL) patients and to investigate whether the results of these scans influenced treatment decisions. PATIENTS: and Methods: In this observational study, we analyzed patients with CLL or small lymphocytic leukemia (SLL) who underwent at least one PET/CT scan from 2007 to 2018. Patients were divided into two groups: (1) patients who had at least one fluorodeoxyglucose-avid PET/CT scan, and (2) patients who had all negative scans. PET/CT results were retrieved from patients' medical files and were revised by an expert radiologist according to visual score scale, SUVmax/SUVliver mean ratio, and the SUVmax. RESULTS: Of the 524 patients, 160 patients (30.5%) had PET/CT scans, and 120 patients met the inclusion criteria. A total of 219 eligible scans were analyzed; 62 of these scans (28.3%) were reported as positive, and 167 of these scans (76.3%) were performed for staging. There was a significant association between PET/CT results and change of therapy (P < .001); however, 62.9% of the positive PET/CT scans were not followed by a change of treatment. Survival time was not different between the two groups. The SUVmax/SUVliver mean ratio was negatively significantly associated with lymphocytes percent (r = -0.237, P = .042) and positively associated with lactate dehydrogenase levels (r = 0.338, P = .008) among CLL patients. CONCLUSION: Despite the fact that the use of surveillance PET/CT for patients with CLL/SLL is not in the guidelines and that it is not useful for disease management, in practice the test is in frequent use in Israel.

Evaluation of the Diagnostic Performance of Positron Emission Tomography/Magnetic Resonance for the Diagnosis of Liver Metastases.

OBJECTIVE: The aim of this study was to compare the performance of positron emission tomography (PET)/magnetic resonance (MR) versus stand-alone PET and stand-alone magnetic resonance imaging (MRI) in the detection and characterization of suspected liver metastases. MATERIALS AND METHODS: This multi-institutional retrospective performance study was approved by the institutional review boards and was Health Insurance Portability and Accountability Act compliant, with waiver of informed consent. Seventy-nine patients with confirmed solid extrahepatic malignancies who underwent upper abdominal PET/MR between February 2017 and June 2018 were included. Where focal hepatic lesions were identified, the likelihood of a diagnosis of a liver metastasis was defined on an ordinal scale for MRI, PET, and PET/MRI by 3 readers: 1 nuclear medicine physician and 2 radiologists. The number of lesions per patient, lesion size, and involved hepatic segments were recorded. Proof of metastases was based on histopathologic correlation or clinical/imaging follow-up. Diagnostic performance was assessed using sensitivity, specificity, positive and negative predictive values, and receiver operator characteristic curve analysis. RESULTS: A total of 79 patients (53 years, interquartile range, 50-68; 43 men) were included. PET/MR had a sensitivity of 95%, specificity of 97%, positive predictive value of 97%, and negative predictive value of 95%. The sensitivity, specificity, positive predictive value, and negative predictive value of MRI were 88%, 98%, 98%, and 90% and for PET were 83%, 97%, 97%, and 86%, respectively. The areas under the curve for PET/MRI, MRI, and PET were 95%, 92%, and 92%, respectively. CONCLUSIONS: Contrast-enhanced PET/MR has a higher sensitivity and negative predictive value than either PET or MRI alone in the setting of suspected liver metastases. Fewer lesions were characterized as indeterminate by PET/MR in comparison with PET and MRI. This superior performance could potentially impact treatment and management decisions for patients with suspected liver metastases.

Axillary Lymph Nodes Hypermetabolism After BNT162b2 mRNA COVID-19 Vaccination in Cancer Patients Undergoing 18F-FDG PET/CT: A Cohort Study.

PURPOSE: Recognition of the pattern of FDG uptake in hypermetabolic axillary lymph nodes (HALs) and association with recent messenger RNA (mRNA) vaccination are important to prevent patient anxiety and further needless examinations or costly biopsies in cancer patients. MATERIALS AND METHODS: This study was a retrospective cohort study in a single tertiary care institution. We investigate the occurrence and pattern of HAL on FDG PET/CT scans from 650 consecutive cancer patients with recent BNT162b2 mRNA COVID-19 vaccination. RESULTS: Between December 20, 2020, and February 8, 2021, 650 patients (351 female patients [54%]; mean age, 68.9 years) had recent mRNA COVID-19 vaccination and an FDG PET/CT scan. HALs were found in 57 (14.5%) of 394 patients (95% confidence interval [CI], 10.9%-18.7%) 12.3 ± 5.9 (1-22) days after dose 1 and in 111 (43.3%) of 256 patients (95% CI, 35.3%-52.2%; P < 0.0001) after 7.5 ± 5.4 (1-22) days after dose 2. There was no difference between dose 1 and dose 2 concerning SUVmax (3.7 ± 1.8 [1.3-11.3] and 4.5 ± 3.9 [1.4-26.3], P = 0.13, respectively), SUVmean (2.1 ± 1.0 [0.7-6.5] and 2.7 ± 2.4 [0.8-17], P = 0.08, respectively), and reactogenicity volume (2.7 ± 2.3 [0.2-11.6] cm3 and 2.7 ± 2.4 [0.2-15.5] cm3, P = 0.98, respectively). There was no difference in number and in size of positive lymph nodes between dose 1 and dose 2: 3.2 ± 2.2 (1-10) and 3.7 ± 2.4 (1-12) (P = 0.18), and 1.4 ± 0.4 cm (0.7-2.5 cm) and 1.5 ± 0.4 cm (0.6-3.2 cm) (P = 0.75), respectively. CONCLUSIONS: A cluster pattern of hypermetabolic ipsilateral small axillary lymph nodes is common after mRNA COVID-19 vaccination, mainly after the second injection.

Novel nanotech antioxidant cocktail prevents medical diagnostic procedures ionizing radiation effects.

Ionizing radiation (IR) exposure results in oxidative damage causing cytotoxic and genotoxic effects. Double-strand breaks (DSBs) are considered the most significant DNA lesions induced by ionizing radiation. The present study evaluates the radio protective effect of a novel antioxidant cocktail through quantification of DSB in peripheral blood lymphocytes (PBL) in vivo. The study included 16 consecutive patients who were divided into 2 groups, 6 patients received the novel antioxidant cocktail and 10 control patients. Blood samples were drawn from the patients undergoing bone scan, before the injection of the 99mTc MDP tracer and 2 h after the injection. Quantification of the IR damage was done by Immunofluorescence analysis of the phosphorylated histone, γ-H2AX, used to monitor DSB induction and repair in PBL. The radiation effect of the control group was measured by 2 variables, the average DBSs foci per nucleus and the percent of the DSB bearing cells in PBL. The findings showed a significant increase in the DSBs after isotope injection with an average increment of 0.29 ± 0.13 of foci/nucleus and 17.07% ± 7.68 more DSB bearing cells (p < 0.05). The cocktail treated group showed a lower difference average of - 2.79% ± 6.13 DSB bearing cells. A paired t-test revealed a significant difference between the groups (p < 0.005) confirming the cocktail's protective effect. The novel anti-oxidant treatment decreases the oxidative stress-induced DNA damage and can be considered as a preventative treatment before radiation exposure.

An international expert opinion statement on the utility of PET/MR for imaging of skeletal metastases.

BACKGROUND: MR is an important imaging modality for evaluating musculoskeletal malignancies owing to its high soft tissue contrast and its ability to acquire multiparametric information. PET provides quantitative molecular and physiologic information and is a critical tool in the diagnosis and staging of several malignancies. PET/MR, which can take advantage of its constituent modalities, is uniquely suited for evaluating skeletal metastases. We reviewed the current evidence of PET/MR in assessing for skeletal metastases and provided recommendations for its use. METHODS: We searched for the peer reviewed literature related to the usage of PET/MR in the settings of osseous metastases. In addition, expert opinions, practices, and protocols of major research institutions performing research on PET/MR of skeletal metastases were considered. RESULTS: Peer-reviewed published literature was included. Nuclear medicine and radiology experts, including those from 13 major PET/MR centers, shared the gained expertise on PET/MR use for evaluating skeletal metastases and contributed to a consensus expert opinion statement. [18F]-FDG and non [18F]-FDG PET/MR may provide key advantages over PET/CT in the evaluation for osseous metastases in several primary malignancies. CONCLUSION: PET/MR should be considered for staging of malignancies where there is a high likelihood of osseous metastatic disease based on the characteristics of the primary malignancy, hight clinical suspicious and in case, where the presence of osseous metastases will have an impact on patient management. Appropriate choice of tumor-specific radiopharmaceuticals, as well as stringent adherence to PET and MR protocols, should be employed.

PET/MRI assessment of lung nodules in primary abdominal malignancies: sensitivity and outcome analysis.

PURPOSE: To evaluate PET/MR lung nodule detection compared to PET/CT or CT, to determine growth of nodules missed by PET/MR, and to investigate the impact of missed nodules on clinical management in primary abdominal malignancies. METHODS: This retrospective IRB-approved study included [18F]-FDG PET/MR in 126 patients. All had standard of care chest imaging (SCI) with diagnostic chest CT or PET/CT within 6 weeks of PET/MR that served as standard of reference. Two radiologists assessed lung nodules (size, location, consistency, position, and [18F]-FDG avidity) on SCI and PET/MR. A side-by-side analysis of nodules on SCI and PET/MR was performed. The nodules missed on PET/MR were assessed on follow-up SCI to ascertain their growth (≥ 2 mm); their impact on management was also investigated. RESULTS: A total of 505 nodules (mean 4 mm, range 1-23 mm) were detected by SCI in 89/126 patients (66M:60F, mean age 60 years). PET/MR detected 61 nodules for a sensitivity of 28.1% for patient and 12.1% for nodule, with higher sensitivity for > 7 mm nodules (< 30% and > 70% respectively, p < 0.05). 75/337 (22.3%) of the nodules missed on PET/MR (follow-up mean 736 days) demonstrated growth. In patients positive for nodules at SCI and negative at PET/MR, missed nodules did not influence patients' management. CONCLUSIONS: Sensitivity of lung nodule detection on PET/MR is affected by nodule size and is lower than SCI. 22.3% of missed nodules increased on follow-up likely representing metastases. Although this did not impact clinical management in study group with primary abdominal malignancy, largely composed of extra-thoracic advanced stage cancers, with possible different implications in patients without extra-thoracic spread.

Impact of PET/MRI in the Treatment of Pancreatic Adenocarcinoma: a Retrospective Cohort Study.

PURPOSE: Imaging is central to the diagnosis and management of Pancreatic Ductal Adenocarcinoma (PDAC). This study evaluated if positron emission tomography (PET)/magnetic resonance imaging (MRI) elicited treatment modifications in PDAC when compared to standard of care imaging (SCI). PROCEDURES: This retrospective study included consecutive patients with PDAC who underwent 2-deoxy-2-[18F]fluoro-D-glucose ([18F]F-FDG) PET/MRI and SCI from May 2017 to January 2019. SCI included abdominal computed tomography (CT), MRI, and/or PET/CT. For patients who had more than one pair of PET/MRI and SCI, each management decision was independently evaluated. Treatment strategies based on each modality were extracted from electronic medical records. Follow-up was evaluated until January 2020. RESULTS: Twenty-five patients underwent 37 PET/MRI's, mean age was 65 ± 9 years and 13 (13/25, 52 %) were men. 49 % (18/37, 95 % CI 33-64 %) of the PET/MRI scans changed clinical management. Whether the SCI included a PET/CT or not did not significantly modify the probability of management change (OR = 0.9, 95 % CI 0.2-4, p = 1). One hundred percent (33/33) of the available follow-up data confirmed PET/MRI findings. CONCLUSIONS: PET/MRI significantly changed PDAC management, consistently across the different SCI modalities it was compared to. These findings suggest a role for PET/MRI in the management of PDAC.

Dynamic 68Ga-PSMA-11 PET/CT for the Primary Evaluation of Localized Renal Mass: A Prospective Study.

The potential role of prostate-specific membrane antigen (PSMA) PET/CT in non-prostate cancer tumors has shown promising results. We examined the performance of dynamic 68Ga-PSMA-11 PET/CT (DPSMA) for the evaluation of localized renal mass. Methods: A prospective case series of patients with a newly diagnosed renal mass who were referred for surgery was examined. DPSMA was performed in a standardized manner before surgery. The final surgical histology served as the standard of reference. PSMA expression in the tumor vasculature was assessed and staining intensity was scored. Tracer uptake and PSMA expression were compared between benign and malignant tissue. Results: Of 29 enhancing renal masses evaluated in 27 patients, 24 (83%) were malignant lesions. The median SUVmean of benign and malignant lesions was 2.3 (interquartile range [IQR], 2.2-2.7) and 6.8 (IQR, 4.2-10.1), respectively (P = 0.009). Median SUVmax of benign and malignant lesions was 3.8 (IQR, 3.3-4.5) and 9.4 (IQR, 5.4-15.8), respectively (P = 0.015). The median washout coefficient (K2) was significantly lower in malignant lesions than in benign lesions (0.17 vs. 0.70, P = 0.02). Positive PSMA staining was found in 20 of 24 malignant lesions and in 2 of 5 benign lesions (P = 0.04). Conclusion: This pilot study demonstrated DPSMA uptake and kinetics in localized renal masses. Increased 68Ga-PSMA-11 tracer uptake and intratumoral retention correlate with PSMA expression in malignant renal tumors compared with benign renal masses, supporting further assessment of DPSMA as a potential tool for evaluating localized renal masses.