Dawn Holley

The potential of TOF PET-MRI for reducing artifacts in PET images

Here we evaluated the potential of TOF PET/MRI to reduce various PET image artifacts, by comparing the images to non-TOF PET/MRI, TOF PET/CT and non-TOF PET/CT.

Biodistribution and radiation dosimetry of 18F-FTC-146 in humans

The purpose of this study was to assess safety, biodistribution, and radiation dosimetry in humans for the highly selective σ-1 receptor PET agent 18F-6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one (18F-FTC-146). Methods: Ten healthy volunteers (5 women, 5 men; age ± SD, 34.3 ± 6.5 y) were recruited, and written informed consent was obtained from all participants. Series of whole-body PET/MRI examinations were acquired for up to 3 h after injection (357.2 ± 48.8 MBq). Blood samples were collected, and standard vital signs (heart rate, pulse oximetry, and body temperature) were monitored at regular intervals. Regions of interest were delineated, time–activity curves were calculated, and organ uptake and dosimetry were estimated. Results: All subjects tolerated the PET/MRI examination well, and no adverse reactions to 18F-FTC-146 were reported. High accumulation of 18F-FTC-146 was observed in σ-1 receptor–dense organs such as the pancreas and spleen, moderate uptake in the brain and myocardium, and low uptake in bone and muscle. High uptake was also observed in the kidneys and bladder, indicating renal tracer clearance. The effective dose of 18F-FTC-146 was 0.0259 ± 0.0034 mSv/MBq (range, 0.0215–0.0301 mSv/MBq). Conclusion: First-in-human studies with clinical-grade 18F-FTC-146 were successful. Injection of 18F-FTC-146 is safe, and absorbed doses are acceptable. The potential of 18F-FTC-146 as an imaging agent for a variety of neuroinflammatory diseases is currently under investigation.

Long-Delay Arterial Spin Labeling Provides More Accurate Cerebral Blood Flow Measurements in Moyamoya Patients: A Simultaneous Positron Emission Tomography/MRI Study.

Background and Purpose— Arterial spin labeling (ASL) MRI is a promising, noninvasive technique to image cerebral blood flow (CBF) but is difficult to use in cerebrovascular patients with abnormal, long arterial transit times through collateral pathways. To be clinically adopted, ASL must first be optimized and validated against a reference standard in these challenging patient cases. Methods— We compared standard-delay ASL (post-label delay=2.025 seconds), multidelay ASL (post-label delay=0.7–3.0 seconds), and long-label long-delay ASL acquisitions (post-label delay=4.0 seconds) against simultaneous [15O]-positron emission tomography (PET) CBF maps in 15 Moyamoya patients on a hybrid PET/MRI scanner. Dynamic susceptibility contrast was performed in each patient to identify areas of mild, moderate, and severe time-to-maximum (Tmax) delays. Relative CBF measurements by each ASL scan in 20 cortical regions were compared with the PET reference standard, and correlations were calculated for areas with moderate and severe Tmax delays. Results— Standard-delay ASL underestimated relative CBF by 20% in areas of severe Tmax delays, particularly in anterior and middle territories commonly affected by Moyamoya disease (P<0.001). Arterial transit times correction by multidelay acquisitions led to improved consistency with PET, but still underestimated CBF in the presence of long transit delays (P=0.02). Long-label long-delay ASL scans showed the strongest correlation relative to PET, and there was no difference in mean relative CBF between the modalities, even in areas of severe delays. Conclusions— Post-label delay times of ≥4 seconds are needed and may be combined with multidelay strategies for robust ASL assessment of CBF in Moyamoya disease.

Semiquantitative Assessment of 18F-FDG Uptake in the Normal Skeleton: Comparison Between PET/CT and Time-of-Flight Simultaneous PET/MRI

OBJECTIVE Differences in the attenuation correction methods used in PET/CT scanners versus the newly introduced whole-body simultaneous PET/MRI reportedly result in differences in standardized uptake values (SUVs) in the normal skeleton. The aim of the study was to compare the semiquantitative FDG uptake in the normal skeleton using time-of-flight (TOF) PET/MRI versus PET/CT with and without TOF. SUBJECTS AND METHODS Participants received a single FDG injection and underwent non-TOF and TOF PET/CT (n = 23) or non-TOF PET/CT and TOF PET/MRI (n = 50). Mean SUV (SUVmean) and maximum SUV (SUVmax) were measured from all PET scans for nine normal regions of the skeleton. Pearson correlation coefficients (r) were used to evaluate the SUVmax and SUVmean of normal skeleton between non-TOF and TOF PET/CT, as well as between non-TOF PET/CT and TOF PET/MRI. In addition, percentage differences in SUVmax and SUVmean of the normal skeleton between non-TOF and TOF PET/CT and between non-TOF PET/CT and TOF PET/MRI were evaluated. RESULTS The SUVmax and SUVmean in the normal skeleton significantly increased between non-TOF and TOF PET/CT, but they significantly decreased between non-TOF PET/CT and TOF PET/MRI. The SUVmax and SUVmean in normal skeleton showed good correlation between non-TOF PET/CT and TOF PET/MRI (SUVmax, r = 0.88; SUVmean, r = 0.91) and showed a similar trend between non-TOF and TOF PET/CT (SUVmax, r = 0.88; SUVmean, r = 0.94). CONCLUSION In the normal skeleton, SUVmax and SUVmean showed high correlations between PET/MRI and PET/CT. The MRI attenuation correction used in TOF PET/MRI provides reliable semiquantitative measurements in the normal skeleton.

[18F]FDG PET/MRI of patients with chronic pain alters management: early experience

The chronic pain sufferer is currently faced with a lack of objective tools to identify the source of their pain. The overarching goal is to develop clinical [18F]FDG PET/MRI methods to more accurately localize sites of increased neuronal and muscular metabolism or inflammation as it relates to neurogenic sources of pain and to ultimately improve outcomes of chronic pain sufferers. The aims are to 1) correlate imaging findings with location of pain symptomology, 2) predict location of symptoms based on imaging findings alone and 3) to determine whether the imaging results affect current management decisions. Six patients suffering from chronic lower extremity neuropathic pain (4 complex regional pain syndrome, 1 chronic sciatica and 1 neuropathic pain) have been imaged with a PET/MRI system (time-of-flight PET; 3.0T bore) from mid thorax through the feet. All patients underwent PET/MR imaging one hour after a injection of 10mCi [18F]FDG. Two radiologists evaluated PET/MR images (one blinded and the other unblinded to patient exam/history). ROI analysis showed focal increased [18F]FDG uptake in affected nerves and muscle (approx 2-4 times more) over background tissue in various regions of the body in 5 of 6 patients at the site of greatest pain symptoms and other areas of the body (SUVmax of Target 0.9-4.2 vs. Background 0.2-1.2). The radiologist blind to the patient history/exam was able to correctly identify side/location of the symptoms in 5 out of 6 patients. Imaging results were reviewed with the referring physician, who then determined whether a modification in the management plan was needed: 1/6 no change, 2/6 mild modification (e.g., additional diagnostic test ordered) and 3/6 significant modification.

Assessment of PET & ASL metabolism in the hippocampal subfields of MCI and AD using simultaneous PET-MR.

Alzheimer’s disease (AD) has been reported to show decreased metabolic activity in the hippocampus using FDG PET-MR. Histological data suggests that the hippocampal subfields are selectively affected in AD. Given the simultaneous imaging nature of integrated PET-MR scanners and the multimodal capabilities of PET-MR, our purpose here is to assess FDG activity, as well as ASL perfusion in the subfields of MCI and AD patients. 10 consecutive subjects were recruited for this study 3 MCI, 3 AD patients and 4 age-matched controls. The scanning was performed on a simultaneous 3T PET/MR scanner. To delineate the hippocampal subfields, automatic segmentation of hippocampal subfields (ASHS) was employed. Static FDG-PET series were reconstructed for analysis at 45-75 min for all subjects. All imaging sequences were automatically registered to the oblique coronal T2-weighted images (segmentation space). PET standardized uptake values (SUV) in the hippocampal subfields were normalized by the pons. FDG PET metabolism was reduced significantly in AD, as well as MCI patients as compared to controls, with the highest effect demonstrated in the CA3/DG and CA1/2 (p = 0.047, subfields. Patients (MCI and AD combined) had decreased metabolism as compared to controls in CA1/2 and significantly smaller volumes the Subiculum. When assessing CBF across groups, a significant decrease in CBF was found in the Subiculum. Our preliminary results demonstrate that PET-MRI may potentially be a sensitive biomarker and tool for early diagnosis of AD. They also confirm the importance of assessing metabolic and structural changes of neurodegenerative diseases at the subfield level.

Correlation between arterial spin labeling MRI and dynamic FDG on PET-MR in Alzheimer’s disease and non-Alzhiemer’s disease patients

Regional hypoperfusion on Arterial Spin Labeling (ASL) MRI and corresponding regions of hypometabolism on FDG PET have been reported in Alzheimer’s Disease (AD). To our knowledge these correlations have not been studied under simultaneous acquisition. The purpose of this study is to investigate the correlation of ASL with FDG PET under simultaneous acquisition on PET-MR and to explore this correlation as a possible biomarker for AD. Dynamic FDG and ASL imaging was performed using a simultaneous TOF-enabled PET-MR scanner in 7 subjects without AD and 3 subjects with AD. Average age was 68±5 years. Automated atlas-based segmentation was performed using T2 MRI using the Talairach atlas. Quantitative analysis of ASL and FDG (delayed 45-75 minute scan) was performed in five regions using the pons as a reference region for both perfusion and metabolism. Statistical analyses included Spearman’s correlation and student’s t-test. Significant correlation of relative perfusion and metabolism was found in two of the five brain regions including the putamen (p = 0.018) and the hippocampus (p = 0.031). In addition, there was significant difference between the relative perfusion and metabolism of the thalamus (p = 0.04). No difference was seen between the AD and non-AD groups. Simultaneous PET-MR demonstrates a positive correlation of perfusion of ASL with metabolism on FDG PET in the hippocampus and putamen. The putamen correlation has previously been reported in the literature on a non-simultaneous ASL and FDG imaging. The thalamus was noted to have a difference in the relative perfusion and metabolism representing a perfusion-metabolism mismatch. Future studies should explore the correlation in additional brain regions and the meaning of perfusion-metabolism mismatches as potential imaging biomarkers for patients with and without AD.

18F-FDG PET/MRI in Chronic Sciatica: Early Results Revealing Spinal and Non-spinal Abnormalities

Chronic sciatica is a major cause of disability worldwide, but accurate diagnosis of the causative pathology remains challenging. In this report, the feasibility of an 18F-FDG PET/MRI approach for improved diagnosis of chronic sciatica is presented. Methods: 18F-FDG PET/MRI was performed on 9 chronic sciatica patients and 5 healthy volunteers (healthy controls). Region-of-interest analysis using SUVmax was performed, and 18F-FDG uptake in lesions was compared with that in the corresponding areas in healthy controls. Results: Significantly increased 18F-FDG uptake was observed in detected lesions in all patients and was correlated with pain symptoms. 18F-FDG–avid lesions not only were found in impinged spinal nerves but also were associated with nonspinal causes of pain, such as facet joint degeneration, pars defect, or presumed scar neuroma. Conclusion: The feasibility of 18F-FDG PET/MRI for diagnosing pain generators in chronic sciatica was demonstrated, revealing various possible etiologies.

Conspicuity of Malignant Lesions on PET/CT and Simultaneous Time-Of-Flight PET/MRI.

Purpose To compare the conspicuity of malignant lesions between FDG PET/CT and a new simultaneous, time-of-flight (TOF) enabled PET/MRI scanner. Methods All patients underwent a single-injection of FDG, followed by a dual imaging protocol consisting of PET/CT followed by TOF PET/MRI. PET/CT and PET/MRI images were evaluated by two readers independently for areas of FDG uptake compatible with malignancy, and then categorized into 5 groups (1: PET/MRI and PET/CT positive; 2: PET/MRI positive, PET/CT positive in retrospect; 3: PET/CT positive, PET/MRI positive in retrospect; 4: PET/MRI positive, PET/CT negative; 5: PET/MRI negative, PET/CT positive) by consensus. Patients with no lesions on either study or greater than 10 lesions based on either modality were excluded from the study. Results Fifty-two patients (mean±SD age: 58±14 years) underwent the dual imaging protocol; of these, 29 patients with a total of 93 FDG-avid lesions met the inclusion criteria. The majority of lesions (56%) were recorded prospectively in the same location on PET/CT and PET/MRI. About an equal small fraction of lesions were seen on PET/CT but only retrospectively on PET/MRI (9%) and vice versa (12%). More lesions were identified only on PET/MRI but not on PET/CT, even in retrospect (96% vs. 81%, respectively; p = 0.003). Discrepant lesions had lower maximum standardized uptake value (SUVmax) than concordant lesions on both modalities (p<0.001). Conclusions While most lesions were identified prospectively on both modalities, significantly more lesions were identified with PET/MRI than with PET/CT.

18F-FDG and Amyloid PET in Dementia

We present a case of memory loss and aphasia in a 72-y-old man and discuss how PET imaging supported a diagnosis of Alzheimer dementia despite conflicting clinical findings.