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Multimodality Imaging of Danon Disease in a Patient with a Novel LAMP2 Mutation [Case Report]

McLeod, Jennifer M; Fowler, Steven J; Cerrone, Marina; Aizer, Anthony; Chinitz, Larry A; Raad, Roy; Saric, Muhamed
PMID: 31709377
ISSN: 2468-6441
CID: 4184922

Simultaneous Evaluation of Lung Anatomy and Ventilation Using 4D Respiratory-Motion-Resolved Ultrashort Echo Time Sparse MRI

Feng, Li; Delacoste, Jean; Smith, David; Weissbrot, Joseph; Flagg, Eric; Moore, William H; Girvin, Francis; Raad, Roy; Bhattacharji, Priya; Stoffel, David; Piccini, Davide; Stuber, Matthias; Sodickson, Daniel K; Otazo, Ricardo; Chandarana, Hersh
BACKGROUND:Computed tomography (CT) and spirometry are the current standard methods for assessing lung anatomy and pulmonary ventilation, respectively. However, CT provides limited ventilation information and spirometry only provides global measures of lung ventilation. Thus, a method that can enable simultaneous examination of lung anatomy and ventilation is of clinical interest. PURPOSE/OBJECTIVE:To develop and test a 4D respiratory-resolved sparse lung MRI (XD-UTE: eXtra-Dimensional Ultrashort TE imaging) approach for simultaneous evaluation of lung anatomy and pulmonary ventilation. STUDY TYPE/METHODS:Prospective. POPULATION/METHODS:In all, 23 subjects (11 volunteers and 12 patients, mean age = 63.6 ± 8.4). FIELD STRENGTH/SEQUENCE/UNASSIGNED:3T MR; a prototype 3D golden-angle radial UTE sequence, a Cartesian breath-hold volumetric-interpolated examination (BH-VIBE) sequence. ASSESSMENT/RESULTS:All subjects were scanned using the 3D golden-angle radial UTE sequence during normal breathing. Ten subjects underwent an additional scan during alternating normal and deep breathing. Respiratory-motion-resolved sparse reconstruction was performed for all the acquired data to generate dynamic normal-breathing or deep-breathing image series. For comparison, BH-VIBE was performed in 12 subjects. Lung images were visually scored by three experienced chest radiologists and were analyzed by two observers who segmented the left and right lung to derive ventilation parameters in comparison with spirometry. STATISTICAL TESTS/UNASSIGNED:Nonparametric paired two-tailed Wilcoxon signed-rank test; intraclass correlation coefficient, Pearson correlation coefficient. RESULTS:XD-UTE achieved significantly improved image quality compared both with Cartesian BH-VIBE and radial reconstruction without motion compensation (P < 0.05). The global ventilation parameters (a sum of the left and right lung measures) were in good correlation with spirometry in the same subjects (correlation coefficient = 0.724). There were excellent correlations between the results obtained by two observers (intraclass correlation coefficient ranged from 0.8855-0.9995). DATA CONCLUSION/UNASSIGNED:Simultaneous evaluation of lung anatomy and ventilation using XD-UTE is demonstrated, which have shown good potential for improved diagnosis and management of patients with heterogeneous lung diseases. LEVEL OF EVIDENCE/METHODS:2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
PMID: 30252989
ISSN: 1522-2586
CID: 3314262

Comparison of hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging and positron emission tomography/computed tomography for evaluation of peripheral nerve sheath tumors in patients with neurofibromatosis type 1

Raad, Roy A; Lala, Shailee; Allen, Jeffrey C; Babb, James; Mitchell, Carole Wind; Franceschi, Ana M; Yohay, Kaleb; Friedman, Kent P
Rapidly enlarging, painful plexiform neurofibromas (PN) in neurofibromatosis type 1 (NF1) patients are at higher risk for harboring a malignant peripheral nerve sheath tumor (MPNST). Fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has been used to support more invasive diagnostic and therapeutic interventions. However, PET/CT imparts an untoward radiation hazard to this population with tumor suppressor gene impairment. The use of FDG PET coupled with magnetic resonance imaging (MRI) rather than CT is a safer alternative but its relative diagnostic sensitivity requires verification. Ten patients (6 females, 4 males, mean age 27 years, range 8-54) with NF1 and progressive PN were accrued from our institutional NF Clinic. Indications for PET scanning included increasing pain and/or progressive disability associated with an enlarging PN on serial MRIs. Following a clinically indicated whole-body FDG PET/CT, a contemporaneous PET/MRI was obtained using residual FDG activity with an average time interval of 3-4 h FDG-avid lesions were assessed for both maximum standardized uptake value (SUVmax) from PET/CT and SUVmax from PET/MR and correlation was made between the two parameters. 26 FDG avid lesions were detected on both PET/CT and PET/MR with an accuracy of 100%. SUVmax values ranged from 1.4-10.8 for PET/CT and from 0.2-5.9 for PET/MRI. SUVmax values from both modalities demonstrated positive correlation (r = 0.45, P < 0.001). PET/MRI radiation dose was significantly lower (53.35% ± 14.37% [P = 0.006]). In conclusion, PET/MRI is a feasible alternative to PET/CT in patients with NF1 when screening for the potential occurrence of MPNST. Reduction in radiation exposure approaches 50% compared to PET/CT.
PMID: 30505221
ISSN: 1450-1147
CID: 3520172

Visual detection of regional brain hypometabolism in cognitively impaired patients is independent of positron emission tomography-magnetic resonance attenuation correction method

Franceschi, Ana M; Abballe, Valentino; Raad, Roy A; Nelson, Aaron; Jackson, Kimberly; Babb, James; Vahle, Thomas; Fenchel, Matthias; Zhan, Yiqiang; Valadez, Gerardo Hermosillo; Shepherd, Timothy M; Friedman, Kent P
Fluorodeoxyglucose (FDG) positron emission tomography-magnetic resonance (PET/MR) is useful for the evaluation of cognitively-impaired patients. This study aims to assess two different attenuation correction (AC) methods (Dixon-MR and atlas-based) versus index-standard computed tomography (CT) AC for the visual interpretation of regional hypometabolism in patients with cognitive impairment. Two board-certified nuclear medicine physicians blindly scored brain region FDG hypometabolism as normal versus hypometabolic using two-dimensional (2D) and 3D FDG PET/MR images generated by MIM software. Regions were quantitatively assessed as normal versus mildly, moderately, or severely hypometabolic. Hypometabolism scores obtained using the different methods of AC were compared, and interreader, as well as intra-reader agreement, was assessed. Regional hypometabolism versus normal metabolism was correctly classified in 16 patients on atlas-based and Dixon-based AC map PET reconstructions (vs. CT reference AC) for 94% (90%-96% confidence interval [CI]) and 93% (89%-96% CI) of scored regions, respectively. The averaged sensitivity/specificity for detection of any regional hypometabolism was 95%/94% (P = 0.669) and 90%/91% (P = 0.937) for atlas-based and Dixon-based AC maps. Interreader agreement for detection of regional hypometabolism was high, with similar outcome assessments when using atlas- and Dixon-corrected PET data in 93% (Κ =0.82) and 93% (Κ =0.84) of regions, respectively. Intrareader agreement for detection of regional hypometabolism was high, with concordant outcome assessments when using atlas- and Dixon-corrected data in 93%/92% (Κ =0.79) and 92/93% (Κ =0.78). Despite the quantitative advantages of atlas-based AC in brain PET/MR, routine clinical Dixon AC yields comparable visual ratings of regional hypometabolism in the evaluation of cognitively impaired patients undergoing brain PET/MR and is similar in performance to CT-based AC. Therefore, Dixon AC is acceptable for the routine clinical evaluation of dementia syndromes.
PMID: 30034284
ISSN: 1450-1147
CID: 3215992

Serial immunological parameters in a phase II trial of exemestane and low-dose oral cyclophosphamide in advanced hormone receptor-positive breast cancer

Kwa, Maryann; Li, Xiaochun; Novik, Yelena; Oratz, Ruth; Jhaveri, Komal; Wu, Jennifer; Gu, Ping; Meyers, Marleen; Muggia, Franco; Speyer, James; Iwano, Alyssa; Bonakdar, Maryam; Kozhaya, Lina; Tavukcuoglu, Ece; Budan, Bahar; Raad, Roy; Goldberg, Judith D; Unutmaz, Derya; Adams, Sylvia
BACKGROUND AND PURPOSE: Resistance to endocrine therapies in hormone receptor (HR)-positive breast cancer is a significant challenge. Prior studies have shown that low-dose oral cyclophosphamide can transiently deplete regulatory T cells (Tregs) and improve anti-tumor immunity. We investigated the combination of exemestane with cyclophosphamide in patients with advanced HR-positive breast cancer and assessed changes in circulating immune cell subsets. METHODS: This was a single-arm phase II trial of exemestane with cyclophosphamide in patients with metastatic HR-positive/HER2-negative breast cancer who had progressed on prior endocrine therapy ( NCT01963481). Primary endpoint was progression-free survival (PFS) at 3 months (RECIST 1.1). Secondary objectives included median PFS, objective response rate, duration of response, and safety. Circulating Tregs (FOXP3+Helios+) and other immune cell subsets were monitored during treatment and compared with healthy controls. RESULTS: Twenty-three patients were enrolled. Treatment was well tolerated, without grade 4/5 toxicities. Objective responses were seen in 6/23 patients (26.1%; 95% CI 10.2-48.4%) and were durable (median 11.6 months). Three-month PFS rate was 50.1% (95% CI 33.0-76.0%); median PFS was 4.23 months (95% CI 2.8-11.7). No treatment-related decrease in Tregs was observed. However, elevated baseline levels of Naive Tregs [greater than 2.5 (the median of the naive Tregs)] were associated with relative risk of disease progression or death [hazard ratio 11.46 (95% CI 2.32-56.5)]. In addition, the baseline levels of Naive Tregs (adj-p = 0.04), Memory Tregs (adj-p = 0.003), CD4 + Central Memory T cells (adj-p = 0.0004), PD-1 + CD4 + Central Memory T cells (adj-p = 0.008), and PD-1 + CD4 + Effector Memory T cells (adj-p = 0.009) were significantly greater in the patients than in the healthy controls; the baseline levels of %CD4 + Naive T cells (adj-p = 0.0004) were significantly lower in patients compared with healthy controls (n = 40). CONCLUSION: Treg depletion was not observed with low-dose cyclophosphamide when assessed by the specific marker FOXP3 + Helios +; however, baseline naive Tregs were associated with 3-month PFS. Exemestane/cyclophosphamide combination had favorable safety profile with evidence of clinical activity in heavily pretreated patients.
PMID: 29124456
ISSN: 1573-7217
CID: 2772912

Coronary artery calcification is common on nongated chest computed tomography imaging

Balakrishnan, Revathi; Nguyen, Brian; Raad, Roy; Donnino, Robert; Naidich, David P; Jacobs, Jill E; Reynolds, Harmony R
BACKGROUND: Coronary artery calcification as assessed by computed tomography (CT) is a validated predictor of cardiovascular risk, whether identified on a dedicated cardiac study or on a routine non-gated chest CT. The prevalence of incidentally detected coronary artery calcification on non-gated chest CT imaging and consistency of reporting have not been well characterized. HYPOTHESIS: Coronary calcification is present on chest CT in some patients not taking statin therapy and may be under-reported. METHODS: Non-gated chest CT images dated 1/1/2012 to 1/1/2013 were retrospectively reviewed. Demographics and medical history were obtained from charts. Patients with known history of coronary revascularization and/or pacemaker/defibrillator were excluded. Two independent readers with cardiac CT expertise evaluated images for the presence and anatomical distribution of any coronary calcification, blinded to all clinical information including CT reports. Original clinical CT reports were subsequently reviewed. RESULTS: Coronary calcification was identified in 204/304 (68%) chest CTs. Patients with calcification were older and had more hyperlipidemia, smoking history, and known coronary artery disease. Of patients with calcification, 43% were on aspirin and 62% were on statin medication at the time of CT. Coronary calcification was identified in 69% of reports when present. CONCLUSIONS: A high prevalence of coronary calcification was found in non-gated chest CT scans performed for non-cardiac indications. In one-third, coronary calcification was not mentioned in the clinical report when actually present. In this population of patients with cardiac risk factors, standard reporting of the presence of coronary calcification may provide an opportunity for risk factor modification.
PMID: 28300293
ISSN: 1932-8737
CID: 2490052

Ipilimumab-Induced Organizing Pneumonia on 18F-FDG PET/CT in a Patient With Malignant Melanoma

Raad, Roy A; Kannan, Rajni; Madden, Kathleen; Pavlick, Anna
A 60-year-old woman with history of vaginal malignant melanoma and inguinal nodal metastases underwent F-FDG PET/CT for restaging following ipilimumab (Yervoy) immunotherapy, a Food and Drug Administration-approved human monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4. PET/CT demonstrated mildly FDG-avid multifocal enlarging bilateral lung opacities. Within each lung lesion, there was circumferential uptake localizing to a high-attenuation rim with a photopenic ground-glass center on CT, consistent with "reversed halo sign." Patient was asymptomatic at the time of imaging. Ipilimumab was discontinued, and 3-month follow-up PET/CT revealed spontaneous complete resolution of the lung lesions, supporting the diagnosis of ipilimumab-induced organizing pneumonia.
PMID: 28481788
ISSN: 1536-0229
CID: 2548852

Ganglion Cyst on 131I Whole-Body Scintigraphy

Khasgiwala, Anunita; Friedman, Kent P; Ghesani, Munir; Raad, Roy A
Interpretation of iodine I whole-body scintigraphy can be challenging, as there are many nonpathologic findings that may present with increased radiotracer uptake. Radiotracer uptake has been reported in the literature involving the salivary glands, thymus, renal cysts, skin contamination, and other benign etiologies. We present the case of an incidental right wrist ganglion cyst demonstrating persistent increased uptake on I whole-body scintigraphy.
PMID: 27775934
ISSN: 1536-0229
CID: 2288592

Prospective Pilot Study to Evaluate the Incremental Value of PET Information in Patients With Bladder Cancer Undergoing 18F-FDG Simultaneous PET/MRI

Rosenkrantz, Andrew B; Friedman, Kent P; Ponzo, Fabio; Raad, Roy A; Jackson, Kimberly; Huang, William C; Balar, Arjun V
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.
PMID: 27775939
ISSN: 1536-0229
CID: 2288602

Comparison of Whole-Body F FDG PET/MR Imaging and Whole-Body F FDG PET/CT in Terms of Lesion Detection and Radiation Dose in Patients with Breast Cancer

Melsaether, Amy N; Raad, Roy A; Pujara, Akshat C; Ponzo, Fabio D; Pysarenko, Kristine M; Jhaveri, Komal; Babb, James S; Sigmund, Eric E; Kim, Sungheon G; Moy, Linda A
Purpose To compare fluorine 18 (18F) fluorodeoxyglucose (FDG) combined positron emission tomography (PET) and magnetic resonance (MR) imaging with 18F FDG combined PET and computed tomography (CT) in terms of organ-specific metastatic lesion detection and radiation dose in patients with breast cancer. Materials and Methods From July 2012 to October 2013, this institutional review board-approved HIPAA-compliant prospective study included 51 patients with breast cancer (50 women; mean age, 56 years; range, 32-76 years; one man; aged 70 years) who completed PET/MR imaging with diffusion-weighted and contrast material-enhanced sequences after unenhanced PET/CT. Written informed consent for study participation was obtained. Two independent readers for each modality recorded site and number of lesions. Imaging and clinical follow-up, with consensus in two cases, served as the reference standard. Results There were 242 distant metastatic lesions in 30 patients, 18 breast cancers in 17 patients, and 19 positive axillary nodes in eight patients. On a per-patient basis, PET/MR imaging with diffusion-weighted and contrast-enhanced sequences depicted distant (30 of 30 [100%] for readers 1 and 2) and axillary (eight of eight [100%] for reader 1, seven of eight [88%] for reader 2) metastatic disease at rates similar to those of unenhanced PET/CT (distant metastatic disease: 28 of 29 [96%] for readers 3 and 4, P = .50; axillary metastatic disease: seven of eight [88%] for readers 3 and 4, P > .99) and outperformed PET/CT in the detection of breast cancer (17 of 17 [100%] for readers 1 and 2 vs 11 of 17 [65%] for reader 3 and 10 of 17 [59%] for reader 4; P < .001). PET/MR imaging showed increased sensitivity for liver (40 of 40 [100%] for reader 1 and 32 of 40 [80%] for reader 2 vs 30 of 40 [75%] for reader 3 and 28 of 40 [70%] for reader 4; P < .001) and bone (105 of 107 [98%] for reader 1 and 102 of 107 [95%] for reader 2 vs 106 of 107 [99%] for reader 3 and 93 of 107 [87%] for reader 4; P = .012) metastases and revealed brain metastases in five of 51 (10%) patients. PET/CT trended toward increased sensitivity for lung metastases (20 of 23 [87%] for reader 1 and 17 of 23 [74%] for reader 2 vs 23 of 23 [100%] for reader 3 and 22 of 23 [96%] for reader 4; P = .065). Dose reduction averaged 50% (P < .001). Conclusion In patients with breast cancer, PET/MR imaging may yield better sensitivity for liver and possibly bone metastases but not for pulmonary metastases, as compared with that attained with PET/CT, at about half the radiation dose. (c) RSNA, 2016 Online supplemental material is available for this article.
PMID: 27023002
ISSN: 1527-1315
CID: 2059122