PET-MRI Research Articles

Abstract PO5-07-11: Use of 64Cu-DOTA trastuzumab -PET to predict response to trastuzumab-deruxtecan (TDXd) in patients with metastatic disease to the brain: Study in Progress

Abstract Background: We have utilized 64Cu-DOTA trastuzumab-PET imaging in patients with advanced breast cancer. In our experience, uptake on 64Cu-DOTA trastuzumab-PET correlated with the qualitative assessment of HER2 by IHC. In women treated with the antibody-drug conjugate (ADC), ado-trastuzumab emtansine (TDM1), we identified a threshold level of 64Cu-DOTA trastuzumab-PET uptake that predicted for lack of response to TDM1. As patients are living longer with advanced breast cancer, the incidence of brain metastasis has increased. The ADC, trastuzumab-deruxtecan (T-DXd) has demonstrated activity in patients with metastatic HER2 positive breast cancer with brain metastases. The DESTINY 04 trial included patients with HER2 1+ and 2+ disease and demonstrated superior survival compared to standard of care. It is not feasible to biopsy all brain metastases to determine tumor markers. Given the increased incidence of brain metastases in this population and the efficacy of T-DXd in patients with HER2+ metastatic disease to the brain, we initiated a study of 64Cu-DOTA trastuzumab-PET/MRI of the brain prior to institution of T-Dxd. Endpoints Primary: 1. 64Cu-DOTA-trastuzumab PET-CT will identify tumor heterogeneity of trastuzumab uptake in women with metastatic breast cancers. 2. The degree of uptake of 64Cu-DOTA-trastuzumab PET-CT will predict for response to Enhertu. Secondary: 1. Uptake of 64Cu-DOTA-trastuzumab PET-CT will be predictive of response duration to Enhertu. Eligibility: Patients must have documented recurrent breast cancer that is HER2 1+, 2+ or 3+, evidence of brain metastases by CT or MRI of the brain and are candidate for treatment with trastuzumab-deruxtecan. The CNS disease must be stable and not in need of intervention. Methods: Prior to treatment staging workups includes pathologic review of HER2 status, disease staging with 18FDG-PET or CT of the chest/abdomen/pelvis and bone scan, and 64Cu-DOTA-trastuzumab PET/MRI of the brain. After initiation of T-Dxd, MRI of the brain is repeated every 6 weeks for the first 24 weeks and every 9 weeks thereafter. Progress: We have enrolled 1 patients to date, received PET and dynamic contrast-enhanced MRI. Four lesions were analyzed in this patient. The mean values of Ktrans (volumetric perfusion to tumor, s−1) in these lesions near a prior resection cavity were 0.210 s−1, indicating sufficient perfusion for ADC uptake. Corresponding to this perfusion data, the mean SUVmax of these lesions on the 64Cu-DOTA-trastuzumab PET scans was 5.38. Citation Format: Joanne Mortimer, Kofi Poku, Jessica Liu, Russell Rockne, Chen Bihong, Ryan Woodall, Vikram Adhikarla. Use of 64Cu-DOTA trastuzumab -PET to predict response to trastuzumab-deruxtecan (TDXd) in patients with metastatic disease to the brain: Study in Progress [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-07-11.

Abstract 2021: 18 F-Sodium Fluoride Positron Emission Tomography To Assess Thoracic Aortopathy In Bicuspid Aortic Valve Disease

Background: Bicuspid aortic valve is associated with thoracic aortopathy with many patients suffering aortic dissection below the aortic diameter threshold for prophylactic aortic replacement surgery. In aortopathy, the aortic wall media initially undergoes increasing microcalcification due to elastin fibre fragmentation but with disease progression, elastin fibre degradation leads to loss of aortic microcalcification. 18 F-Sodium fluoride positron emission tomography (PET) is a non-invasive method of detecting arterial microcalcification that has been successfully used in cardiovascular disease risk stratification. Aims: To determine if aortic 18 F-sodium fluoride imaging can identify aortopathy and predict subsequent disease progression in patients with bicuspid aortic valve disease. Methods: In this prospective cohort study, 77 patients with bicuspid aortic valve from clinical sites across Scotland and 18 healthy volunteers, underwent 18 F-sodium fluoride PET-computed tomography (PET-CT) followed immediately by PET-magnetic resonance imaging (PET-MRI). Maximum standardised uptake values (SUVmax) were determined in the ascending aorta. Aortic diameters were measured in aortic axial CINE MRI sequences. Patients were followed-up at 24 months with a further PET-MRI. Annualised change in aortic size index (mm/m 2 /year) and annualised change in SUVmax stratified in tertiles were calculated. Results: Patients with bicuspid aortic valve disease had higher SUVmax than control subjects, especially in those with aortic dilatation. Baseline SUVmax was associated with annualised aortic expansion rate independent of baseline aortic size (β=0.45, p=0.001). Patients in tertile 1 (loss of SUVmax over time) exhibited greater aortic growth (0.60±0.50 mm/m 2 /year) than those with stable SUVmax (tertile 2, 0.26±0.36 mm/m 2 /year) or increasing SUVmax (tertile 3, 0.24±0.36 mm/m 2 /year; p=0.01). Conclusion: Aortic microcalcification activity is increased in aortopathy of patients with bicuspid aortic valve. Loss of aortic microcalcification is associated with more rapid disease progression and represents a promising new approach to the identification of patients at higher risk of aortic complications.

Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study

In people with genetic forms of Alzheimer's disease, such as in Down syndrome and autosomal-dominant Alzheimer's disease, pathological changes specific to Alzheimer's disease (ie, accumulation of amyloid and tau) occur in the brain at a young age, when comorbidities related to ageing are not present. Studies including these cohorts could, therefore, improve our understanding of the early pathogenesis of Alzheimer's disease and be useful when designing preventive interventions targeted at disease pathology or when planning clinical trials. We compared the magnitude, spatial extent, and temporal ordering of tau spread in people with Down syndrome and autosomal-dominant Alzheimer's disease. In this cross-sectional observational study, we included participants (aged ≥25 years) from two cohort studies. First, we collected data from the Dominantly Inherited Alzheimer's Network studies (DIAN-OBS and DIAN-TU), which include carriers of autosomal-dominant Alzheimer's disease genetic mutations and non-carrier familial controls recruited in Australia, Europe, and the USA between 2008 and 2022. Second, we collected data from the Alzheimer Biomarkers Consortium-Down Syndrome study, which includes people with Down syndrome and sibling controls recruited from the UK and USA between 2015 and 2021. Controls from the two studies were combined into a single group of familial controls. All participants had completed structural MRI and tau PET (18F-flortaucipir) imaging. We applied Gaussian mixture modelling to identify regions of high tau PET burden and regions with the earliest changes in tau binding for each cohort separately. We estimated regional tau PET burden as a function of cortical amyloid burden for both cohorts. Finally, we compared the temporal pattern of tau PET burden relative to that of amyloid. We included 137 people with Down syndrome (mean age 38·5 years [SD 8·2], 74 [54%] male, and 63 [46%] female), 49 individuals with autosomal-dominant Alzheimer's disease (mean age 43·9 years [11·2], 22 [45%] male, and 27 [55%] female), and 85 familial controls, pooled from across both studies (mean age 41·5 years [12·1], 28 [33%] male, and 57 [67%] female), who satisfied the PET quality-control procedure for tau-PET imaging processing. 134 (98%) people with Down syndrome, 44 (90%) with autosomal-dominant Alzheimer's disease, and 77 (91%) controls also completed an amyloid PET scan within 3 years of tau PET imaging. Spatially, tau PET burden was observed most frequently in subcortical and medial temporal regions in people with Down syndrome, and within the medial temporal lobe in people with autosomal-dominant Alzheimer's disease. Across the brain, people with Down syndrome had greater concentrations of tau for a given level of amyloid compared with people with autosomal-dominant Alzheimer's disease. Temporally, increases in tau were more strongly associated with increases in amyloid for people with Down syndrome compared with autosomal-dominant Alzheimer's disease. Although the general progression of amyloid followed by tau is similar for people Down syndrome and people with autosomal-dominant Alzheimer's disease, we found subtle differences in the spatial distribution, timing, and magnitude of the tau burden between these two cohorts. These differences might have important implications; differences in the temporal pattern of tau accumulation might influence the timing of drug administration in clinical trials, whereas differences in the spatial pattern and magnitude of tau burden might affect disease progression. None.

MRI and 18F-FET PET for Multimodal Treatment Monitoring in Patients with Brain Metastases: A Cost-Effectiveness Analysis.

PET using the radiolabeled amino acid O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) has been shown to be of value for treatment monitoring in patients with brain metastases after multimodal therapy, especially in clinical situations with equivocal MRI findings. As medical procedures must be justified socioeconomically, we determined the effectiveness and cost-effectiveness of 18F-FET PET for treatment monitoring of multimodal therapy, including checkpoint inhibitors, targeted therapies, radiotherapy, and combinations thereof in patients with brain metastases secondary to melanoma or non-small cell lung cancer. Methods: We analyzed already-published clinical data and calculated the associated costs from the German statutory health insurance system perspective. Two clinical scenarios were considered: decision tree model 1 determined the effectiveness of 18F-FET PET alone for identifying treatment-related changes, that is, the probability of correctly identifying patients with treatment-related changes confirmed by neuropathology or clinicoradiographically using the Response Assessment in Neuro-Oncology criteria for immunotherapy. The resulting cost-effectiveness ratio showed the cost for each correctly identified patient with treatment-related changes in whom MRI findings remained inconclusive. Decision tree model 2 calculated the effectiveness of both 18F-FET PET and MRI, that is, the probability of correctly identifying nonresponders to treatment. The incremental cost-effectiveness ratio was calculated to determine cost-effectiveness, that is, the cost for each additionally identified nonresponder by 18F-FET PET who would have remained undetected by MRI. One-way deterministic and probabilistic sensitivity analyses tested the robustness of the results. Results: 18F-FET PET identified 94% of patients with treatment-related changes, resulting in €1,664.23 (€1.00 = $1.08 at time of writing) for each correctly identified patient. Nonresponders were correctly identified in 60% by MRI and in 80% by 18F-FET PET, resulting in €3,292.67 and €3,915.83 for each correctly identified nonresponder by MRI and 18F-FET PET, respectively. The cost to correctly identify 1 additional nonresponder by 18F-FET PET, who would have remained unidentified by MRI, was €5,785.30. Conclusion: Given the considerable annual cost of multimodal therapy, the integration of 18F-FET PET can potentially improve patient care while reducing costs.

Extranodal natural killer/T cell lymphoma of the skeletal muscle.

This case report highlights a case of extranodal NK/T cell lymphoma initially misdiagnosed as myositis, emphasizing the appearance on both MRI and FDG PET images. The patient presented with systemic symptoms and calf muscle swelling, prompting imaging studies that revealed diffuse muscle involvement. Despite negative myositis markers and inconclusive biopsy, post-amputation findings confirmed lymphoma with EBV positivity. The appearance in both MRI and FDG PET complicated the diagnostic process, underscoring the importance of considering lymphoma in cases of muscle-related symptoms to prevent delays in appropriate management. This case contributes to the understanding of the diagnostic challenges associated with extranodal NK/T cell lymphoma and emphasizes the significance of peripheral band-like features in imaging studies.

In vivo translocator protein in females with autism spectrum disorder: a pilot study

Sex-based differences in the prevalence of autism spectrum disorder (ASD) are well-documented, with a male-to-female ratio of approximately 4:1. The clinical presentation of the core symptoms of ASD can also vary between sexes. Previously, positron emission tomography (PET) studies have identified alterations in the in vivo levels of translocator protein (TSPO)—a mitochondrial protein—in primarily or only male adults with ASD, with our group reporting lower TSPO relative to whole brain mean in males with ASD. However, whether in vivo TSPO levels are altered in females with ASD, specifically, is unknown. This is the first pilot study to measure in vivo TSPO in the brain in adult females with ASD using [11C]PBR28 PET-magnetic resonance imaging (MRI). Twelve adult females with ASD and 10 age- and TSPO genotype-matched controls (CON) completed one or two [11C]PBR28 PET–MRI scans. Females with ASD exhibited elevated [11C]PBR28 standardized uptake value ratio (SUVR) in the midcingulate cortex and splenium of the corpus callosum compared to CON. No brain area showed lower [11C]PBR28 SUVR in females with ASD compared to CON. Test-retest over several months showed stable [11C]PBR28 SUVR across time in both groups. Elevated regional [11C]PBR28 SUVR in females with ASD stand in stark contrast to our previous findings of lower regional [11C]PBR28 SUVR in males with ASD. Preliminary evidence of regionally elevated mitochondrial protein TSPO relative to whole brain mean in ASD females may reflect neuroimmuno-metabolic alterations specific to females with ASD.

State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms.

Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.

Abstract LB419: Neuroinflammation and aromatase inhibitor associated musculoskeletal syndrome (AIMSS) in breast cancer: Initial insights from [11C]PBR28 PET/MR imaging

Abstract Introduction: While 5-10 years of aromatase inhibitor (AI) treatment clearly improves survival rates of postmenopausal women with hormone-sensitive breast cancer, up to 85% of AI users report aromatase inhibitor associated musculoskeletal syndrome (AIMSS, including arthralgias, myalgias, and muscle stiffness). The biological mechanisms underlying AIMSS are not well understood, but accumulating preclinical and clinical evidence implicate an important role for neuroinflammation in the development and maintenance of other types of chronic musculoskeletal pain (e.g., low back pain, fibromyalgia etc.). The purpose of this pilot study was to investigate the role of neuroinflammation in breast cancer patients with AIMSS. Methods: This cross-sectional case control study used Siemens 3 T integrated positron emission tomography-magnetic resonance imaging (PET/MRI) with the radioligand [11C]PBR28, which binds to the neuroinflammation marker 18kDa translocator protein (TSPO), to assess neuroinflammation in two cohorts (chronic AIMSS, no-AIMSS) of breast cancer patients undergoing AI therapy, and age-, sex- and TSPO genotype-matched healthy controls. Static [11C]PBR28 PET images were reconstructed from 60-90 minutes post-injection. Standardized uptake value (SUV) maps were obtained voxel-wise by normalizing radioactivity by injected dose/body weight. SUV maps were normalized to whole brain to obtain SUV ratio (SUVR) maps. SUVR images spatially normalized to MNI template and then spatially smoothed (FWHM=8mm). Results: Two breast cancer patients (1 AIMSS, 1 no-AIMSS) and 2 matched healthy controls were included in this analysis. Compared to their individual matched healthy controls, both breast cancer patients showed increased [11C]PBR28 signal uptake in the thalamus/midbrain and pons. This elevated signal was more prominent in the breast cancer patient with AIMSS. Conclusions: These preliminary findings suggest an elevated signal of neuroinflammation in the thalamus and brainstem in AI-treatment and AIMSS, aligning with existing literature emphasizing their pivotal role in chronic pain pathology. While it is imperative to acknowledge the limitation of a small sample size, these promising findings suggest a potential role of neuroinflammation for the first time in AIMSS. Future focused Region of Interest (ROI) analysis in thalamus and brainstem with a larger sample size may confirm. Citation Format: Yehui Zhu, Natalie Swanson, Jennifer Murphy, Minhae Kim, Ann Partridge, Robert Edwards, Kristin Schreiber, Marco Loggia. Neuroinflammation and aromatase inhibitor associated musculoskeletal syndrome (AIMSS) in breast cancer: Initial insights from [11C]PBR28 PET/MR imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB419.

Early-phase amyloid PET reproduces metabolic signatures of cognitive decline in Parkinson's disease.

Recent work suggests that amyloid beta (Aβ) positron emission tomography (PET) tracer uptake shortly after injection ("early phase") reflects brain metabolism and perfusion. We assessed this modality in a predominantly amyloid-negative neurodegenerative condition, Parkinson's disease (PD), and hypothesized that early-phase 18F-florbetaben (eFBB) uptake would reproduce characteristic hypometabolism and hypoperfusion patterns associated with cognitive decline in PD. One hundred fifteen PD patients across the spectrum of cognitive impairment underwent dual-phase Aβ PET, structural and arterial spin labeling (ASL) magnetic resonance imaging (MRI), and neuropsychological assessments. Multiple linear regression models compared eFBB uptake to cognitive performance and ASL MRI perfusion. Reduced eFBB uptake was associated with cognitive performance in brain regions previously linked to hypometabolism-associated cognitive decline in PD, independent of amyloid status. Furthermore, eFBB uptake correlated with cerebral perfusion across widespread regions. EFBB uptake is a potential surrogate measure for cerebral perfusion/metabolism. A dual-phase PET imaging approach may serve as a clinical tool for assessing cognitive impairment. Images taken at amyloid beta (Aβ) positron emission tomography tracer injection may reflect brain perfusion and metabolism.Parkinson's disease (PD) is a predominantly amyloid-negative condition.Early-phase florbetaben (eFBB) in PD was associated with cognitive performance.eFBB uptake reflects hypometabolism-related cognitive decline in PD.eFBB correlated with arterial spin labeling magnetic resonance imaging measured cerebral perfusion.eFBB distinguished dementia from normal cognition and mild cognitive impairment.Findings were independent of late-phase Aβ burden.Thus, eFBB may serve as a surrogate measure for brain metabolism/perfusion.

1132 Phase 1 Correlates of Seizure Onset Zone for Prediction of sEEG Placement and Clinical Outcomes

INTRODUCTION: Approximately 20 million people worldwide suffer from drug resistant epilepsy. Treatment of the seizure onset zone (SOZ) can reduce seizure burden. When phase 1 testing fails to identify a clear surgical lesion, stereo-electroencephalography (sEEG) offers a high-resolution spatial map of cortical and subcortical activity. However, each additional lead placed also increases the chances of a complication. Preoperative identification of optimal targets is crucial to minimizing the risk-benefit ratio of sEEG placement. METHODS: We studied epilepsy patients that underwent sEEG placement followed by resection, stimulation, or laser ablation at a single institution from 1/2012 to 11/2021. Leads were identified by their respective Phase 1 indications. Preoperative and 1-year postoperative clinical outcomes were compared. Hypothesis testing was performed via the Wilcoxon rank sum test and Fisher’s exact test. A logistic generalized linear mixed effect model was used for multivariate analysis. RESULTS: 101 patients had 1752 leads placed with 239 SOZs found and treated. Mean weekly seizure frequency decreased from 25.2 to 7.8 (p < 0.001). SOZ leads were more likely to have concordant findings (p < 0.001) across studies. Lesions with PET hypometabolism (OR 1.4), MRI abnormalities (OR 1.9), MEG Clusters (OR 1.9) and calcifications (OR 3.2) were significantly more likely to predict SOZ, though PET hypometabolism was not significant in multivariate analysis. While the reason for lead placement in the SOZ did not predict seizure outcomes, patients with other lesions that had MEG Clusters or Calcifications had an average 15% worse seizure reduction than those without (p < 0.005). CONCLUSIONS: Certain Phase 1 aspects of a putative lesion, such as MRI abnormalities, the presence of calcifications, or MEG clusters can predict SOZ and clinical outcomes.

Ga68] DOTATATE PET/MRI-guided radiosurgical treatment planning and response assessment in meningiomas.

Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery. Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning. Follow-up DOTATATE PET/MRI was performed at 6-12 months post-radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVRSSS) referencing superior sagittal sinus (SSS) blood pool were obtained. Size change was determined by Response Assessment in Neuro-Oncology (RANO) criteria. Association of SUVRSSS change magnitude and progression-free survival (PFS) was evaluated using Cox regression. Twenty-seven patients with 64 tumors (26% World Health Organization [WHO]-1, 41% WHO-2, 26% WHO-3, and 7% WHO-unknown) were prospectively followed post stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT; mean dose: 30 Gy, modal dose 35 Gy, mean of 5 fractions). Post-irradiation SUV and SUVRSSS decreased by 37.4% and 44.4%, respectively (P < .0001). Size product decreased by 8.9%, thus failing to reach the 25% significance threshold as determined by RANO guidelines. Mean follow-up time was 26 months (range: 6-44). Overall mean PFS was 83% and 100%/100%/54% in WHO-1/-2/-3 subcohorts, respectively, at 34 months. At maximum follow-up (42-44 months), PFS was 100%/83%/54% in WHO-1/-2/-3 subcohorts, respectively. Cox regression analyses revealed a hazard ratio of 0.48 for 10-unit reduction in SUVRSSS in the SRS cohort. DOTATATE PET SUV and SUVRSSS demonstrated marked, significant decrease post-radiosurgery. Lesion size decrease was statistically significant; however, it was not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising imaging biomarker for response assessment in meningiomas treated with radiosurgery. NCT04081701.

Diffuse lymphoma involvement of the spinal cord showed on [18F]FDG PET/MRI.

A 61-year-old woman with diffuse large B-cell lymphoma received a fluorine-18-deoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) for staging. Because of the obvious uptake of [¹⁸F]FDG in the spinal cord and brain, a positron emission tomography/magnetic resonance imaging (PET/MRI) was performed after the positron emission tomography/computed tomography (PET/CT). The images showed diffuse [¹⁸F]FDG uptake of the spinal cord and increased T2 signal intensity on MRI, which was suspected to be lymphoma involvement. The patient was diagnosed with diffuse large B-cell lymphoma involving the right maxillofacial region, right cervical lymph nodes, cervix, brain and spinal cord (stage IV of non-germinal center B-cell origin). After chemotherapy, the spinal [¹⁸F]FDG uptake level decreased significantly, which was considered to be a partial metabolic response. Our case was different from prior, which indicated the pattern of spinal cord involvement by lymphoma was focal.

Cerebral Tau Deposition in Comorbid Progressive Supranuclear Palsy and Amyotrophic Lateral Sclerosis: An [18F]-Flortaucipir and 7T MRI Study

Introduction: Progressive supranuclear palsy (PSP) is a four-repeat tauopathy characterized by multiple clinicopathologic subtypes. Advanced neuroimaging techniques have shown an early ability to distinguish PSP subtypes noninvasively for improved diagnosis. This study utilized tau PET imaging and MRI techniques at 7T to determine the neuroimaging profile of a participant with comorbid PSP and amyotrophic lateral sclerosis (ALS). Method: [18F]-flortaucipir PET imaging was performed on one participant with PSP-ALS, one participant with typical PSP (Richardson’s syndrome; PSP-RS), and 15 healthy control volunteers. Standardized uptake value ratio (SUVR) in each brain region was compared between PSP participants and controls. Quantitative susceptibility mapping (QSM) and inflow-based vascular-space occupancy MRI at 7T were performed on the two PSP participants and on two age-matched healthy controls to evaluate for differences in regional brain iron content and arteriolar cerebral blood volume (CBVa), respectively. Results: In the participant with PSP-ALS, the precentral gyrus demonstrated the highest [18F]-flortaucipir uptake of all brain regions relative to controls (z-score 1.94). In the participant with PSP-RS, [18F]-flortaucipir uptake relative to controls was highest in subcortical regions, including the pallidum, thalamus, hippocampus, and brainstem (z-scores 1.08, 1.41, 1.49, 1.32, respectively). Susceptibility values as a measure of brain iron content were higher in the globus pallidus and substantia nigra than in the midbrain and pons in each participant, regardless of group. CBVa values tended to be higher in the subcortical gray matter in PSP participants than in controls, although large measurement variability was noted in controls across multiple regions. Conclusion: In vivo tau PET imaging of an individual with PSP-ALS overlap demonstrated increased tau burden in the motor cortex that was not observed in PSP-RS or control participants. Consistent with prior PET studies, tau burden in PSP-RS was mainly observed in subcortical regions, including the brainstem and basal ganglia. QSM data suggest that off-target binding to iron may account for some but not all of the increased [18F]-flortaucipir uptake in the basal ganglia in PSP-RS. These findings support existing evidence that tau PET imaging can distinguish among PSP subtypes by detecting distinct regional patterns of tau deposition in the brain. Larger studies are needed to determine whether CBVa is sensitive to changes in brain microvasculature in PSP.

A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures

Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. While a direct correlation between seizure duration and the extent of brain injury has been widely reported, there are limited data comparing the neuroprotective efficacy of diazepam versus midazolam following acute OP intoxication. To address this data gap, we used non-invasive imaging techniques to longitudinally quantify neuropathology in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) with and without post-exposure intervention with diazepam or midazolam. Magnetic resonance imaging (MRI) was used to monitor neuropathology and brain atrophy, while positron emission tomography (PET) with a radiotracer targeting translocator protein (TSPO) was utilized to assess neuroinflammation. Animals were scanned at 3, 7, 28, 65, 91, and 168 days post-DFP and imaging metrics were quantitated for the hippocampus, amygdala, piriform cortex, thalamus, cerebral cortex and lateral ventricles. In the DFP-intoxicated rat, neuroinflammation persisted for the duration of the study coincident with progressive atrophy and ongoing tissue remodeling. Benzodiazepines attenuated neuropathology in a region-dependent manner, but neither benzodiazepine was effective in attenuating long-term neuroinflammation as detected by TSPO PET. Diffusion MRI and TSPO PET metrics were highly correlated with seizure severity, and early MRI and PET metrics were positively correlated with long-term brain atrophy. Collectively, these results suggest that anti-seizure therapy alone is insufficient to prevent long-lasting neuroinflammation and tissue remodeling.

Clinical Arterial Spin-Labeling MR Imaging to Screen for Typical and Atypical Neurodegenerative Disease in the New Era of Alzheimer Treatment.

The clinical standard of care in the diagnosis of neurodegenerative diseases relies on [18F] FDG-PET/CT or PET MR imaging. Limitations of FDG-PET include cost, the need for IV access, radiation exposure, and availability. Arterial spin-labeling MR imaging has been shown in research settings to be useful as a proxy for FDG-PET in differentiating Alzheimer disease from frontotemporal dementia. However, it is not yet widely used in clinical practice, except in cerebrovascular disease. Here, we present 7 patients, imaged with our routine clinical protocol with diverse presentations of Alzheimer disease and other neurodegenerative diseases, in whom arterial spin-labeling-derived reduced CBF correlated with hypometabolism or amyloid/tau deposition on PET. Our case series illustrates the clinical diagnostic utility of arterial spin-labeling MR imaging as a fast, accessible, and noncontrast screening tool for neurodegenerative disease. Arterial spin-labeling MR imaging can guide patient selection for subsequent PET or fluid biomarker work-up, as well as for possible therapy with antiamyloid monoclonal antibodies.

Challenges, limitations, and pitfalls of PET and advanced MRI in patients with brain tumors: A report of the PET/RANO group.

Brain tumor diagnostics have significantly evolved with the use of positron emission tomography (PET) and advanced magnetic resonance imaging (MRI) techniques. In addition to anatomical MRI, these modalities may provide valuable information for several clinical applications such as differential diagnosis, delineation of tumor extent, prognostication, differentiation between tumor relapse and treatment-related changes, and the evaluation of response to anticancer therapy. In particular, joint recommendations of the Response Assessment in Neuro-Oncology (RANO) Group, the European Association of Neuro-oncology, and major European and American Nuclear Medicine societies highlighted that the additional clinical value of radiolabeled amino acids compared to anatomical MRI alone is outstanding and that its widespread clinical use should be supported. For advanced MRI and its steadily increasing use in clinical practice, the Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition provided more recently an updated acquisition protocol for the widely used dynamic susceptibility contrast perfusion MRI. Besides amino acid PET and perfusion MRI, other PET tracers and advanced MRI techniques (e.g. MR spectroscopy) are of considerable clinical interest and are increasingly integrated into everyday clinical practice. Nevertheless, these modalities have shortcomings which should be considered in clinical routine. This comprehensive review provides an overview of potential challenges, limitations, and pitfalls associated with PET imaging and advanced MRI techniques in patients with gliomas or brain metastases. Despite these issues, PET imaging and advanced MRI techniques continue to play an indispensable role in brain tumor management. Acknowledging and mitigating these challenges through interdisciplinary collaboration, standardized protocols, and continuous innovation will further enhance the utility of these modalities in guiding optimal patient care.

Radiomics: A Powerful Tool

The Artificial Intelligence based technique of radiomics is an evolving modality that employs data characterization algorithms to extract a variety of useful features from medical images [1].Tumoral patterns are revealed that cannot be appreciated by the naked eye [2]. This can aid in assessing prognosis and gauging the response of tumor cells to therapy [3]. Various imaging modalities like CT, PET MR provide essential raw data. Extraction tools then use the raw data volumes to analyze pixel/voxel characteristics. Using these images, “volumes of interest” can be generated since such segmentation entails handling and processing of large image data; automatic and semiautomatic segmentation algorithms are employed enabling automation [4]. However, thorough testing and quality assurance are vital to ensure that the algorithm used is not only accurate, consistent, and reproducible but also time-efficient [5].

Current Trends and Applications of PET/MRI Hybrid Imaging in Neurodegenerative Diseases and Normal Aging.

Dementia is a significant global health issue that is exacerbated by an aging population. Imaging plays an established role in the evaluation of patients with neurocognitive disorders such as dementia. In current clinical practice, magnetic resonance imaging (MRI) and positron emission tomography (PET) are primary imaging modalities used separately but in concert to help diagnose and classify dementia. The clinical applications of PET/MRI hybrid imaging in dementia are an active area of research, particularly given the continued emergence of functional MRI (fMRI) and amyloid PET tracers. This narrative review provides a comprehensive overview of the rationale and current evidence for PET/MRI hybrid dementia imaging from 2018 to 2023. Hybrid imaging offers advantages in the accuracy of characterizing neurodegenerative disorders, and future research will need to address the cost of integrated PET/MRI systems compared to stand-alone scanners, the development of new biomarkers, and image correction techniques.

Automated detection of Alzheimer’s disease: a multi-modal approach with 3D MRI and amyloid PET

Recent advances in deep learning and imaging technologies have revolutionized automated medical image analysis, especially in diagnosing Alzheimer’s disease through neuroimaging. Despite the availability of various imaging modalities for the same patient, the development of multi-modal models leveraging these modalities remains underexplored. This paper addresses this gap by proposing and evaluating classification models using 2D and 3D MRI images and amyloid PET scans in uni-modal and multi-modal frameworks. Our findings demonstrate that models using volumetric data learn more effective representations than those using only 2D images. Furthermore, integrating multiple modalities enhances model performance over single-modality approaches significantly. We achieved state-of-the-art performance on the OASIS-3 cohort. Additionally, explainability analyses with Grad-CAM indicate that our model focuses on crucial AD-related regions for its predictions, underscoring its potential to aid in understanding the disease’s causes.

Prospective Study to Evaluate the Role of Dual Point Contrast-enhanced Magnetic Resonance Imaging in Differentiation of Brain Tumoral from Nontumoral Tissue: A Magnetic Resonance/PET Study.

Follow-up imaging of gliomas is crucial to look for residual or recurrence and to differentiate them from nontumoral tissue. Positron emission tomography (PET)-magnetic resonance imaging (MRI) is the problem-solving tool in such cases. We investigated the role of dual point contrast (DPC)-enhanced MRI to discriminate tumoral from the nontumoral tissue compared to PET-MRI taken as the gold standard. The institutional ethics committee approved the study, and consent was obtained from all the patients included in the study. We prospectively did immediate and 75-min delayed contrast MRI in glioma cases who came for follow-up as a part of PET-MRI study in our institute. Subtracted images were obtained using immediate and 75-min delayed contrast images. Color-coded subtracted images were compared with PET-MRI images. 75-min delayed contrast MRI and diffusion-weighted imaging (DWI) images with Gray Scale inversion were compared with PET attenuation-corrected images. We included 23 PET MRI cases done with different radiotracers in our study. Overall, we found PET-DPC correlation in (20/20 ~ 100%) cases of enhancing tumors. In two cases (DOPA and fluorodeoxyglucose), since they were nonenhancing low-grade gliomas and the other one was melanoma with intrinsic T1 hyperintensity and the DPC technique could not be used. DWI-PET correlated in 17/19 (~89.4%) cases, and perfusion-weighted imaging (PWI)-PET dynamic susceptibility contrast (DSC)/ASL correlated in 14/18 (~77.7%) cases after cases with hemorrhage were excluded. DPC MRI showed a good correlation with PET MRI in discriminating tumoral from the nontumoral tissue. DPC MRI can act as a potential alternative to PET MRI in peripheral hospitals where PET is not available. However, the DPC technique is limited in low-grade nonenhancing gliomas.