Faculty Bibliography

OBJECTIVES/OBJECTIVE:F-FDG uptake on whole-body PET-CT with MR findings and compare the degree of FDG activity between symptomatic and asymptomatic knees. MATERIALS AND METHODS/METHODS:Retrospective database query was performed using codes for knee MRI as well as whole-body PET-CT. Patients with malignant disease involving the knee or hardware were excluded. Patients who had both studies performed within 1 year between 2012 and 2017 were included for analysis. Knee joint osteoarthrosis, meniscal and ligamentous integrity, presence of joint effusion, and synovitis were assessed and recorded. Bone marrow edema lesions (BMELs) were identified, segmented, and analyzed using volumetric analysis. SUVmax was assessed over the suprapatellar joint space, intercondylar notch and Hoffa's fat pad. Symptomatic and asymptomatic knees were compared in patients with unilateral symptoms. RESULTS:Twenty-two cases (20 patients) with mean age 63.3 years (range, 36-91 years) were included. Two patients had bilateral pain. The most FDG avid regions in both symptomatic and asymptomatic knees were the intercondylar notch (SUVmax = 1.84 vs. 1.51), followed by suprapatellar pouch (SUVmax = 1.74 vs. 1.29) and Hoffa's fat pad (SUVmax = 1.01 vs. 0.87). SUVmax was significantly associated with cartilage loss (mean modified Outerbridge score) (r = 0.60, p = 0.003) and degree of synovitis (r = 0.48, p = 0023). Overall, mean SUVmax was significantly higher in the presence of a meniscal tear (1.83 ± 0.67 vs. 1.22 ± 0.40, p = 0.030). Nine patients had BMELs (volume: range = 0.6-27.8, mean = 7.79) however there was no significant association between BMEL volume and SUVmax. CONCLUSIONS:Higher FDG activity correlates with intra-articular derangement and the intercondylar notch represents the most metabolically active region of the knee.

PURPOSE: To correlate shoulder ultrasound and radiography with F-FDG PET-CT to establish FDG uptake and therefore range of metabolic activity, as defined by SUV analysis, in various symptomatic shoulder pathologies. METHODS: Retrospective database query was performed for shoulder ultrasound and PET-CT scans between January 2012 and January 2017. Patients who had both studies within 1 year were included. Age- and sex-matched control patients with PET-CT scans only were also included. Retrospective image review determined shoulder pathology, and F-FDG SUVmax was measured using regions of interest placed at the glenohumeral joint, rotator cuff/bursa, and bicipital groove. Glenohumeral and acromioclavicular osteoarthrosis was assessed by radiography using the Kellgren-Lawrence classification system. RESULTS: Thirty-three patients had both imaging studies within 1 year. Ten patients (11 cases) were included, ranging in age from 56 to 90 years (mean, 67.9 years). Control subjects were selected among patients receiving PET-CT within 1 week of symptomatic patients. Glenohumeral osteoarthrosis was mild in 3 (27%), moderate in 2 (18%), and severe in 2 (18%). Six full-thickness rotator cuff tears (55%) were identified. SUVmax means were compared between the pathologic and control groups and were significantly higher in the former: glenohumeral joint (1.96 vs 1.32; P = 0.016), rotator cuff/bursa (2.80 vs 2.0; P = 0.005), and bicipital groove (2.19 vs 1.48; P = 0.007). The highest values were seen in full-thickness rotator cuff tear and severe biceps tenosynovitis. CONCLUSIONS: Increased metabolic activity about the shoulder is associated with a spectrum of rotator cuff, glenohumeral joint, and other soft tissue pathology that can be correlated with diagnostic ultrasound findings.

PURPOSE: The aim of this study was to conduct a prospective pilot study comparing the diagnostic performance of MRI alone and F-FDG simultaneous PET/MRI using a diuresis protocol in bladder cancer patients. METHODS: Twenty-two bladder cancer patients underwent F-FDG PET/MRI, using intravenous furosemide and oral hydration for bladder clearance. A radiologist scored probability of tumor in 3 locations (urinary bladder, pelvic lymph nodes, nonnodal pelvis) using 1- to 3-point scale (1 = negative, 2 = equivocal, 3 = definite tumor). A nuclear medicine physician reviewed fused PET/MRI images, after which scores were reassigned based on combined findings. Follow-up pathologic and imaging data served as reference. Performances of MRI alone and PET/MRI were compared. RESULTS: Of these patients, 82%, 38%, and 18% were positive for bladder, pelvic nodal, and nonnodal pelvic tumor, respectively. At a score of 3, PET/MRI exhibited greater accuracy for detection of bladder tumor (86% vs 77%), metastatic pelvic lymph nodes (95% vs 76%), and nonnodal pelvic malignancy (100% vs 91%). In the bladder, PET changed the level of suspicion in 36% of patients (50% increased suspicion, 50% decreased suspicion), with 75% of these changes deemed correct based on reference standard. For pelvic lymph nodes, PET changed suspicion in 52% (36% increase, 64% decrease), with 95% of changes deemed correct. For nonnodal pelvis, PET changed suspicion in 9% (100% increase), with 100% deemed correct. CONCLUSIONS: Additional PET information helped to appropriately determine level of suspicion in multiple anatomic sites for otherwise equivocal findings on MRI alone. Although requiring larger studies, findings suggest a possible role for simultaneous PET/MRI to assist bladder cancer management.

Quantitative standardized uptake values (SUVs) from fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are commonly used to evaluate the extent of disease and response to treatment in breast cancer patients. Recently, PET/magnetic resonance imaging (MRI) has been shown to qualitatively detect metastases from various primary cancers with similar sensitivity to PET/CT. However, quantitative validation of PET/MRI requires assessing the reliability of SUVs from MR attenuation correction (MRAC) relative to CT attenuation correction (CTAC). The purpose of this retrospective study was to assess the utility of PET/MRI-derived SUVs in breast cancer patients by testing the hypothesis that SUVs derived from MRAC correlate well with those from CTAC. Between August 2012 and May 2013, 35 breast cancer patients (age 37-78 years, 1 man) underwent clinical 18F-FDG PET/CT followed by PET/MRI. One hundred seventy metastases were seen in 21 of 35 patients; metastases to bone in 16 patients, to liver in seven patients, and to nonaxillary lymph nodes in eight patients were sufficient for statistical analysis on an organ-specific per patient basis. SUVs in the most FDG-avid metastasis per organ per patient from PET/CT and PET/MRI were measured and compared using Pearson's correlations. Correlations between CTAC- and MRAC-derived SUVmax and SUVmean in 31 metastases to bone, liver, and nonaxillary lymph nodes were strong overall (rho = 0.80, 0.81). SUVmax and SUVmean correlations were also strong on an organ-specific basis in 16 bone metastases (rho = 0.76, 0.74), seven liver metastases (rho = 0.85, 0.83), and eight nonaxillary lymph node metastases (rho = 0.95, 0.91). These strong organ-specific correlations between SUVs from PET/CT and PET/MRI in breast cancer metastases support the use of SUVs from PET/MRI for quantitation of 18F-FDG activity.

PURPOSE: To assess outcomes of lung nodules missed on simultaneous positron emission tomography and magnetic resonance imaging (PET/MRI) compared to the reference standard PET and computed tomography (PET/CT) in patients with primary malignancy. MATERIALS AND METHODS: In all, 208 patients with primary malignancy undergoing clinically indicated (18 F) fluorodeoxyglucose (FDG) PET/CT followed by PET/MRI were independently reviewed by two readers. Upon review of the thoracic station on PET/MRI and PET/CT, 89 non-FDG avid small lung nodules in 43 patients were detected (by reader 1) only on the CT component of the PET/CT but were not identified on PET/MRI. Overall, 84 of these 89 nodules were examined on follow-up imaging with PET/CT or chest CT. The remaining five nodules had no follow-up imaging but had remote imaging available for comparison. RESULTS: Among the 84 nodules with follow-up, three nodules (3%) in one patient progressed, 10 (12%) nodules partially/completely resolved, whereas 71 nodules (85%) remained stable. The five nodules without follow-up were all stable since prior imaging of over 21 months. CONCLUSION: The vast majority (97%) of small non-FDG avid lung nodules missed on PET/MRI either resolved or remained stable on follow-up, suggestive of benignity. PET/MRI remains a viable alternative imaging modality in oncology patients, despite its low sensitivity in detecting small lung nodules. J. Magn. Reson. Imaging 2015.

Purpose: Whole body PET-MRI to evaluate for osseous malignancy is a novel rapidly emerging modality. While several studies have shown the individual utility of Fluorine-18 labelled fluorodeoxyglucose (FDG) and sodium fluoride (NaF) PET tracers and diffusion weighted imaging (DWI) MRI in evaluating metastatic and primary osseous malignancy, there is no literature directly comparing all three parameters using whole body hybrid PET-MRI. The purpose of this pilot study is to directly compare FDG and NaF PET scans and DWI ADC mapping for detecting osseous malignancy on whole body PET-MRI. Materials and Methods: A retrospective review of 8 biopsy proven malignant bone lesions (7 CT guided biopsies and 1 surgical biopsy) and 11 benign bone lesions were evaluated in 13 patients who had whole body FDG PETMRI and/or NaF PET-MRI including DWI with apparent diffusion coefficient (ADC) mapping. For each bone lesion, the SUVmax, ADCmin, and ADCmean was calculated. On PET, criteria for malignancy was prominent focal round or mass-like tracer uptake morphology, and criteria for benign lesion was absence of increased uptake relative to background bone or linear uptake morphology consistent with benign disease. On DWI, criteria for malignancy was ADC value in the range of 0.7 - 1.0 x 10-3 mm2/s as previously published, and criteria for benign was an ADC value outside of this range. The reference standard for malignancy was biopsy results and the reference standard for benign lesion was characteristic benign appearance on conventional MRI sequences (T1, T2, STIR). The sensitivity and specificity of each measurement was calculated. McNemar tests were used to compare diagnostic tests based on each measure in terms of accuracy relative to the reference standard diagnosis. Results: 8 patients (5 females, 3 males, avg. age 60) had malignant bone lesions and 7 patients (3 females, 4 males, avg. age 65) had benign bone lesions which were evaluated. Malignant lesions included four metastatic breast cancer, two metastatic prostate cancer, one multiple myeloma, and one Ewing's sarcoma. Benign lesions included eight degenerative, one fracture, two enthesopathic, one hemangioma, and one avascular necrosis. The sensitivities, specificities, and accuracies of FDG PETwere 50, 50, 50 %, of NaF PETwere 100, 67, 75%, of ADCmin were 88, 100, 95%, of ADCmean were 63, 100, 86 %. Conclusion: Our preliminary data suggests that when using whole body PET-MRI to evaluate for osseous malignancy, NaF may have the highest sensitivity compared to FDG and DWI, and DWI has the highest specificity and accuracy with ADCmin being more accurate than ADCmean. This could be useful clinical information for diagnosis, treatment, surveillance and surgical/biopsy planning and warrants further investigation

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.

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.

Simultaneous positron emission tomography (PET)/magnetic resonance (MR) imaging is a promising novel technology for oncology diagnosis and staging and neurologic and cardiac applications. Our institution's current research protocol results in a total imaging time of approximately 45 to 70 minutes with simultaneous PET/MR imaging, making this a feasible total body imaging protocol. Further development of MR-based attenuation correction will improve PET quantification. Quantitatively accurate multiparametric PET/MR data sets will likely improve diagnosis of disease and help guide and monitor the therapies for individualized patient care.

The purpose of this study is to report further about the statistically significant results from a prospective study, which suggests that fusion of prone F-18 Fluoro-deoxy-glucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) breast scans increases the positive predictive value (PPV) and specificity for patients in whom the MR outcome alone would be nonspecific. Thirty-six women (mean age, 43 years; range, 24-65 years) with 90 lesions detected on MR consented to undergo a FDG-PET scan. Two blinded readers evaluated the MR and the computer tomography (CT) attenuation-corrected prone FDG-PET scans side-by-side, then after the volumes were superimposed (fused). A semiautomatic, landmark-based program was used to perform nonrigid fusion. Pathology and radiologic follow-up were used as the reference standard. The sensitivity, specificity, PPV, negative predictive value (NPV), and accuracy (with 95% confidence intervals) for MR alone, FDG-PET alone, and fused MR and FDG-PET were calculated. The median lesion size measured from the MR was 2.5 cm (range, 0.5-10 cm). Histologically, 56 lesions were malignant, and 15 were benign. Nineteen lesions were benign after 20-47 months of clinical and radiologic surveillance. The sensitivity of MR alone was 95%, FDG-PET alone was 57%, and fusion was 83%. The increase in PPV from 77% in MR alone to 98% when fused and the increase in specificity from 53% to 97% were statistically significant (p < 0.05). The false-negative rate on FDG-PET alone was 26.7%, and after fusion this number was reduced to 9%. FDG-PET and MR fusions were helpful in selecting which lesion to biopsy, especially in women with multiple suspicious MR breast lesions