Faculty Bibliography

Subsolid nodules (SSNs) are increasingly encountered in chest computed tomography (CT) imaging and clinical practice, as awareness of their significance and CT utilization grows. Either part-solid or solely ground-glass in attenuation, SSNs are shown to correlate with lung adenocarcinomas and their precursors, although a differential diagnosis is to be considered that includes additional neoplastic and inflammatory etiologies. This review discusses the differential diagnosis for SSNs, imaging and clinical features, and pathology that are helpful when making management decisions that may include PET/CT, biopsy, or surgery. Potential pitfalls in nodule characterization and management will be highlighted, to aid in managing SSNs appropriately.

OBJECTIVES/OBJECTIVE:To evaluate the yield of CT-guided biopsy of 18F-piflufolastat PET avid osseous lesions in suspected prostate metastases. METHODS:Retrospective review of computed tomography guided biopsies targeting 18F-piflufolastat avid lesions on PET/CT or PET/MR performed between 2022 and 2024. Demographics, image modality, biopsy system, number of cores, lesion location, lean body mass corrected SUV (SUL) and pathology were recorded. Biopsied lesions were compared to the PROMISE (prostate cancer molecular imaging standardized evaluation) scoring system, version 2. RESULTS:Eighteen patients were included, average age 68.7 years. Lesions were defined as: ≥ 50 % sclerotic (n = 10), <50 % sclerotic (n = 7), occult (n = 0), and lytic (n = 1). A technically successful pathologic diagnosis was made in 94 % of biopsies (n = 17). Histopathological diagnosis included: metastatic prostate adenocarcinoma (n = 12), benign with fibrotic/densely sclerotic bone or normocellular bone marrow (n = 5), and metastatic non-small cell lung carcinoma (n = 1). The median SUL on PET for all patients was 7.9 (IQR 13.3), 2.6 (0.3) for benign biopsies, and 8.8 (12.5) for malignant biopsies. Major identifiable differences between biopsies yielding a metastatic versus benign diagnosis included: higher SUL (p-value = 0.03), target lesion volume (p-value = 0.01), and higher incidence of sclerotic lesions (p value = 0.003); however, multivariate analysis did not find these to be statistically significant predictors (p-value >0.05). The prostate cancer lesion biopsy positive group had significantly higher PROMISE scores than the negative group (p = 0.03). CONCLUSION/CONCLUSIONS:CT-guided biopsy of bone lesions demonstrating avidity for 18F-piflufolastat can be performed with a high diagnostic yield.

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.

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.

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.

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 (ClinicalTrials.gov: 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.

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.

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.

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.