Faculty Bibliography

In routine whole-body PET/MR hybrid imaging, attenuation correction (AC) is usually performed by segmentation methods based on a Dixon MR sequence providing up to 4 different tissue classes. Because of the lack of bone information with the Dixon-based MR sequence, bone is currently considered as soft tissue. Thus, the aim of this study was to evaluate a novel model-based AC method that considers bone in whole-body PET/MR imaging. METHODS: The new method ("Model") is based on a regular 4-compartment segmentation from a Dixon sequence ("Dixon"). Bone information is added using a model-based bone segmentation algorithm, which includes a set of prealigned MR image and bone mask pairs for each major body bone individually. Model was quantitatively evaluated on 20 patients who underwent whole-body PET/MR imaging. As a standard of reference, CT-based mu-maps were generated for each patient individually by nonrigid registration to the MR images based on PET/CT data. This step allowed for a quantitative comparison of all mu-maps based on a single PET emission raw dataset of the PET/MR system. Volumes of interest were drawn on normal tissue, soft-tissue lesions, and bone lesions; standardized uptake values were quantitatively compared. RESULTS: In soft-tissue regions with background uptake, the average bias of SUVs in background volumes of interest was 2.4% +/- 2.5% and 2.7% +/- 2.7% for Dixon and Model, respectively, compared with CT-based AC. For bony tissue, the -25.5% +/- 7.9% underestimation observed with Dixon was reduced to -4.9% +/- 6.7% with Model. In bone lesions, the average underestimation was -7.4% +/- 5.3% and -2.9% +/- 5.8% for Dixon and Model, respectively. For soft-tissue lesions, the biases were 5.1% +/- 5.1% for Dixon and 5.2% +/- 5.2% for Model. CONCLUSION: The novel MR-based AC method for whole-body PET/MR imaging, combining Dixon-based soft-tissue segmentation and model-based bone estimation, improves PET quantification in whole-body hybrid PET/MR imaging, especially in bony tissue and nearby soft tissue.

BACKGROUND: An abscopal response describes radiotherapy-induced immune-mediated tumour regression at sites distant to the irradiated field. Granulocyte-macrophage colony-stimulating factor is a potent stimulator of dendritic cell maturation. We postulated that the exploitation of the pro-immunogenic effects of radiotherapy with granulocyte-macrophage colony-stimulating factor might result in abscopal responses among patients with metastatic cancer. METHODS: Patients with stable or progressing metastatic solid tumours, on single-agent chemotherapy or hormonal therapy, with at least three distinct measurable sites of disease, were treated with concurrent radiotherapy (35 Gy in ten fractions, over 2 weeks) to one metastatic site and granulocyte-macrophage colony-stimulating factor (125 mug/m2 subcutaneously injected daily for 2 weeks, starting during the second week of radiotherapy). This course was repeated, targeting a second metastatic site. A Simon's optimal two-stage design was chosen for this trial: an additional 19 patients could be enrolled in stage 2 only if at least one patient among the first ten had an abscopal response. If no abscopal responses were seen among the first ten patients, the study would be deemed futile and terminated. The primary endpoint was the proportion of patients with an abscopal response (defined as at least a 30% decrease in the longest diameter of the best responding abscopal lesion). Secondary endpoints were safety and survival. Analyses were done based on intention to treat. The trial has concluded accrual, and is registered with ClinicalTrials.gov, number NCT02474186. FINDINGS: From April 7, 2003, to April 3, 2012, 41 patients with metastatic cancer were enrolled. In stage 1 of the Simon's two-stage design, ten patients were enrolled: four of the first ten patients had abscopal responses. Thus, the trial proceeded to stage 2, as planned, and an additional 19 patients were enrolled. Due to protocol amendments 12 further patients were enrolled. Abscopal responses occurred in eight (27.6%, 95% CI 12.7-47.2) of the first 29 patients, and 11 (26.8%, 95% CI 14.2-42.9) of 41 accrued patients (specifically in four patients with non-small-cell lung cancer, five with breast cancer, and two with thymic cancer). The most common grade 3-4 adverse events were fatigue (six patients) and haematological (ten patients). Additionally, a serious adverse event of grade 4 pulmonary embolism occurred in one patient. INTERPRETATION: The combination of radiotherapy with granulocyte-macrophage colony-stimulating factor produced objective abscopal responses in some patients with metastatic solid tumours. This finding represents a promising approach to establish an in-situ anti-tumour vaccine. Further research is warranted in this area. FUNDING: New York University School of Medicine's Department of Radiation Oncology and Cancer Institute.

Simultaneous data collection for positron emission tomography and magnetic resonance imaging (PET/MR) is now a reality. While the full benefits of concurrently acquiring PET and MR data and the potential added clinical value are still being evaluated, initial studies have identified several important potential pitfalls in the interpretation of fluorodeoxyglucose (FDG) PET/MRI in oncologic whole-body imaging, the majority of which being related to the errors in the attenuation maps created from the MR data. The purpose of this article was to present such pitfalls and artifacts using case examples, describe their etiology, and discuss strategies to overcome them. Using a case-based approach, we will illustrate artifacts related to (1) Inaccurate bone tissue segmentation; (2) Inaccurate air cavities segmentation; (3) Motion-induced misregistration; (4) RF coils in the PET field of view; (5) B0 field inhomogeneity; (6) B1 field inhomogeneity; (7) Metallic implants; (8) MR contrast agents.

Positron emission tomography (PET) and magnetic resonance imaging, until recently, have been performed on separate PET and MR systems with varying temporal delay between the two acquisitions. The interpretation of these two separately acquired studies requires cognitive fusion by radiologists/nuclear medicine physicians or dedicated and challenging post-processing. Recent advances in hardware and software with introduction of hybrid PET/MR systems have made it possible to acquire the PET and MR images simultaneously or near simultaneously. This review article serves as a road-map for clinical implementation of hybrid PET/MR systems and briefly discusses hardware systems, the personnel needs, safety and quality issues, and reimbursement topics based on experience at NYU Langone Medical Center and Cleveland Clinic.

PURPOSE: The aim of this study was to compare coregistration of the bladder wall, bladder masses, and pelvic lymph nodes between sequential and simultaneous PET and MRI acquisitions obtained during hybrid F-FDG PET/MRI performed using a diuresis protocol in bladder cancer patients. METHODS: Six bladder cancer patients underwent F-FDG hybrid PET/MRI, including IV Lasix administration and oral hydration, before imaging to achieve bladder clearance. Axial T2-weighted imaging (T2WI) was obtained approximately 40 minutes before PET ("sequential") and concurrently with PET ("simultaneous"). Three-dimensional spatial coordinates of the bladder wall, bladder masses, and pelvic lymph nodes were recorded for PET and T2WI. Distances between these locations on PET and T2WI sequences were computed and used to compare in-plane (x-y plane) and through-plane (z-axis) misregistration relative to PET between T2WI acquisitions. RESULTS: The bladder increased in volume between T2WI acquisitions (sequential, 176 [139]mL; simultaneous, 255 [146]mL). Four patients exhibited a bladder mass, all with increased activity (SUV, 9.5-38.4). Seven pelvic lymph nodes in 4 patients showed increased activity (SUV, 2.2-9.9). The bladder wall exhibited substantially less misregistration relative to PET for simultaneous, compared with sequential, acquisitions in in-plane (2.8 [3.1]mm vs 7.4 [9.1]mm) and through-plane (1.7 [2.2]mm vs 5.7 [9.6]mm) dimensions. Bladder masses exhibited slightly decreased misregistration for simultaneous, compared with sequential, acquisitions in in-plane (2.2 [1.4]mm vs 2.6 [1.9]mm) and through-plane (0.0 [0.0]mm vs 0.3 [0.8]mm) dimensions. FDG-avid lymph nodes exhibited slightly decreased in-plane misregistration (1.1 [0.8]mm vs 2.5 [0.6]mm), although identical through-plane misregistration (4.0 [1.9]mm vs 4.0 [2.8]mm). CONCLUSIONS: Using hybrid PET/MRI, simultaneous imaging substantially improved bladder wall coregistration and slightly improved coregistration of bladder masses and pelvic lymph nodes.

OBJECTIVE: The objective of our study was to assess the role of recently introduced hybrid PET/MRI in the evaluation of lymphoma patients using PET/CT as a reference standard. SUBJECTS AND METHODS: In this prospective study 28 consecutive lymphoma patients (18 men, 10 women; mean age, 53.6 years) undergoing clinically indicated PET/ CT were subsequently imaged with PET/MRI using residual FDG activity from the PET/ CT study. Blinded readers evaluated PET/CT (reference standard), PET/MRI, and diffusion-weighted imaging (DWI) studies separately; for each study, they assessed nodal and extranodal involvement. Each FDG-avid nodal station was marked and compared on DWI, PET/MRI, and PET/CT. Modified Ann Arbor staging was performed and compared between PET/MRI and PET/CT. The maximum standardized uptake value (SUVmax) on PET/MRI for FDG-avid nodal lesions was compared with the SUVmax on PET/CT. The apparent diffusion coefficient (ADC) for FDG-avid nodal lesions was compared to SUVmax on PET/MRI. RESULTS: Fifty-one FDG-avid nodal groups were identified on PET/CT in 13 patients. PET/MRI identified 51 of these nodal groups with a sensitivity of 100%. DWI identified 32 nodal groups for a sensitivity of 62.7%. PET/MRI staging and PET/CT staging were concordant in 96.4% of patients. For the one patient with discordant staging results, disease was correctly upstaged to stage IV on the basis of the PET/MRI finding of bone marrow involvement, which was missed on PET/CT. DWI staging was concordant with PET/CT staging in 64.3% of the patients. The increased staging accuracy of PET/MRI relative to DWI was significant (p = 0.004). SUVmax measured on PET/MRI and PET/CT showed excellent statistically significant correlation (r = 0.98, p < 0.001). There was a poor negative correlation between ADC and SUVmax (r = -0.036, p = 0.847). CONCLUSION: PET/MRI can be used to assess disease burden in lymphoma with sensitivity similar to PET/CT and can be a viable alternative for lymphoma staging and follow-up.

A 78-year-old man with metastatic malignant melanoma underwent a restaging 18F-FDG PET/CT after initiation of ipilimumab therapy, a Food and Drug Administration-approved human monoclonal antibody targeting CTLA-4. PET/CT demonstrated intense FDG uptake fusing to poorly circumscribed hypodensities throughout the liver. Patient was experiencing high-grade fever, chills, and generalized fatigue at the time of imaging, as well as mildly elevated liver function tests. Patient was subsequently treated with corticosteroids for suspected ipilimumab-induced hepatitis, and the patient rapidly improved clinically. Follow-up PET/CT 2 months later revealed complete resolution of abnormal FDG uptake in the liver, confirming the diagnosis of ipilimumab-induced hepatitis.

PURPOSE: Dynamic FDG imaging for prostate cancer characterization is limited by generally small size and low uptake in prostate tumors. Our aim in this pilot study was to explore feasibility of simultaneous PET/MRI to guide localization of prostate lesions for dynamic FDG analysis using a graphical approach. METHODS: Three patients with biopsy-proven prostate cancer underwent simultaneous FDG PET/MRI, incorporating dynamic prostate imaging. Histology and multiparametric MRI findings were used to localize tumors, which in turn guided identification of tumors on FDG images. Regions of interest were manually placed on tumor and benign prostate tissue. Blood activity was extracted from a region of interest placed on the femoral artery on PET images. FDG data were analyzed by graphical analysis using the influx constant Ki (Patlak analysis) when FDG binding seemed irreversible and distribution volume VT (reversible graphical analysis) when FDG binding seemed reversible given the presence of washout. RESULTS: Given inherent coregistration, simultaneous acquisition facilitated use of MRI data to localize small lesions on PET and subsequent graphical analysis in all cases. In 2 cases with irreversible binding, tumor had higher Ki than benign using Patlak analysis (0.023 vs 0.006 and 0.019 vs 0.008 mL/cm per minute). In 1 case appearing reversible, tumor had higher VT than benign using reversible graphical analysis (0.68 vs 0.52 mL/cm). CONCLUSIONS: Simultaneous PET/MRI allows localization of small prostate tumors for dynamic PET analysis. By taking advantage of inclusion of the femoral arteries in the FOV, we applied advanced PET data analysis methods beyond conventional static measures and without blood sampling.

Integrated PET/MR with simultaneous acquisition may improve the identification of pathologic findings in patients. This pilot study evaluated metabolic activity differences between epilepsy patients and healthy controls and directly correlated FDG uptake with MR regional abnormality. Epilepsy patients (n=11) and controls (n=6) were imaged on a whole-body simultaneous PET/MR scanner. After FDG injection, simultaneous images were acquired for 60 minutes. Statistical analyses on SUV values (over 117 brain regions, including left and right, for 96 cortical and 21 subcortical regions) derived from three normalization methods, by individual subject's mean cortical, white matter or global brain, were compared between groups. The asymmetry was compared. T2, T1 and PET co-registered images were also used for lesion detection and correlation of PET and MR regional abnormality. Left and right postcentral gyri were found to be consistently hypermetabolic regions, while right temporal pole and planum polare were consistently hypometabolic regions by all three normalization methods. Using the asymmetry index (AI > 10% or SUV ratios > 1.2), more metabolic asymmetry regions were detected in patients than in controls, with 96.2% agreement. The presence of hippocampal abnormalities or cortical tubers detected via T2 FLAIR in patients correlated well with the hypometabolism detected via FDG-PET. Our results showed specific patterns of metabolic abnormality and asymmetry over 117 brain regions in epilepsy patients, as compared to controls, suggest that simultaneous PET/MR imaging provides a useful tool to help understand etiopathogenesis and localize seizure foci.

PURPOSE: Imaging is important to identify subclinical changes and for treatment planning in patients with osteonecrosis of the jaw (ONJ) exposed to antiresorptive therapy. The aim of this study was to compare the findings at radiography with those at fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT) for patients with ONJ related to antiresorptive therapy. MATERIALS AND METHODS: A cross-sectional retrospective analysis of patients with clinically identified ONJ lesions of the mandible was performed. Two imaging modalities were evaluated for each patient: plain radiography (ie, panoramic or periapical) and FDG PET/CT with 1-mm sections. Outcome variables for the radiographic findings were osteolytic and osteosclerotic bone changes. Outcome variables for FDG PET/CT images were localization of FDG uptake. Maximum standard uptake values (SUVmax) of abnormal FDG jaw uptake were recorded, in addition to the mean SUV of the contralateral normal mandible, and used to calculate the target-to-background ratio. Radiographic changes and FDG uptake were classified as local (ie, corresponding to exposed cortical bone) or diffuse (ie, local changes and changes extending beyond the margins of exposed bone) for each imaging technique. Local and diffuse changes detected by each imaging modality were described and the difference in detection was compared with the McNemar test. RESULTS: Twenty-three patients with 25 clinically identified ONJ lesions were analyzed using radiography and FDG PET/CT. Differences were found in how radiography and FDG PET/CT detect local and diffuse changes associated with ONJ. Radiography showed local changes in 17 patients (68%), diffuse changes in 3 patients (12%), and no changes in 5 patients (20%), whereas FDG PET/CT imaging showed local changes in 17 patients (68%) and diffuse changes in 8 patients (32%). The McNemar test indicated that FDG PET/CT imaging was less likely to miss a lesion (P < .001). Mean SUVmax was 6.59, and the mean target-to-background ratio was 5.37. CONCLUSION: The results of this study show that FDG PET/CT detects local and diffuse metabolic changes that may not be represented by plain radiography for patients with ONJ related to antiresorptive therapy. The target-to-background ratio allowed the discrimination between ONJ lesions and background changes. Future studies are necessary to determine whether FDG PET/CT can determine risk and facilitate management of ONJ.