Introduction: Balloon test occlusion (BTO) with adjunctive single-photon emission computed tomography (SPECT) has been utilized to predict clinical tolerance after permanent internal carotid artery (ICA) occlusion. Cerebrovascular anatomical characteristics might predict BTO outcomes and identify patients susceptible to test failure. Methods: We performed a single center retrospective study of patients who underwent catheter based cerebral angiogram and ICA BTO from July 2013 to June 2020. SPECT imaging was completed in all the patients who passed the clinical BTO; technetium 99m-ethyl cysteinate dimer was injected intravenously after 15-30 min of occlusion and induced hypotension. The diameter of each of the vessels of the Circle of Willis was measured angiographically. The severity of hypoperfusion on SPECT imaging was classified as none, mild, low intermediate, high intermediate, and severe. Results: A total of 57 patients underwent BTO; neoplasia was the most common indication (n=43, 75%). Twelve patients (21.1%) developed neurologic symptoms and clinically failed the BTO; 45 patients (78.9%) passed and proceeded to SPECT. Contralateral dominant vertebral artery (p=0.02), smaller ACom (p=0.002) and ipsilateral PCom (p=0.03) diameters were correlated with clinical BTO failure. Smaller ACom was most predictive with an AUC of 0.907. The Youden index identified an ACom diameter threshold of 1.1 mm, which demonstrated a sensitivity of 91.7% and specificity of 77.8% (OR 0.026, 95% CI 0.003 - 0.226, ROC=0.847) for the prediction of BTO failure. Patients with severe SPECT asymmetry had significantly smaller caliber ACom arteries (ACom median diameter 0.95 mm vs. rest of cohort median 1.4; p=0.0073). Conclusions: BTO outcomes may be predicted using angiographic findings. A small (<1.1 mm) anterior communicating artery, and, less significantly, a small ipsilateral posterior communicating artery can be used to identify patients who are likely to fail BTO.

Background Early diagnosis of lupus nephritis (LN) can be challenging since some patients do not exhibit overt clinical manifestations until advanced stages. B cell interferon-beta (IFNβ) correlates with development of B cell autoreactive phenotype. The objective of the present study is to determine if elevated IFNβ in circulating B cells can be a useful indicator for the development of more severe histopathologic features of LN. Methods Flow cytometry was used to quantitate intracellular IFNβ in naive (IgD+CD27−) CD19+ B-cells in the peripheral blood mononuclear cells (PBMCs) of a cross-sectional cohort (N=80) of patients with systemic lupus erythematosus (SLE), 33 of whom had lupus nephritis. Serologic and clinical manifestations of LN included anti-DNA, anti-Sm, C3, C4, and urine protein/creatinine ratio were determined. The correlation of B-cell IFNβ with lupus nephritis classification and histopathological findings, light, electron microscopy, and immunofluorescence (IF) for deposition of IgM, IgG, IgA, C1q, and C3 was determined in 23 of the 33 patients for whom renal biopsy data was available. Results LN was identified in 41% of our cohort of 80 SLE patients. Naïve B-cell IFNβ was positively associated with the development of LN but not cutaneous disease. Higher levels of B-cell IFNβ also correlated with higher levels of circulating anti-dsDNA, anti-Sm, and the urinary protein/creatinine ratio. Biopsy examination revealed that proliferative LN lesions (Class III, IV with or without V) characterized by significantly elevated endocapillary hypercellularity, fibrous crescent, and fibrocellular crescent were significantly associated with high B-cell IFNβ. Surprisingly, IgG, IgA, IgM, C3, and C1q deposition in the kidney was not correlated with B-cell IFNβ. Conclusions Our results suggest that B-cell IFNβ can be used in combination with other clinical diagnostic markers to assist in identifying patients who are at high risk of developing advanced LN. Acknowledgments This work was supported by the VA Merit Review grant [I01BX004049]; the NIH grants [R01-AI-071110, R01 AI134023], the Lupus Research Alliance Distinguished Innovator Award; the LRA Target Identification in Lupus Award; and to support flow cytometry analysis [P30-AR-048311 and P30-AI-027767]. Funders had no role in design, analysis, and reporting.

Background: 23Na MRI correlates with tumor proliferation, and studies in pediatric patients are lacking. The purpose of the study: (1) to compare total sodium concentration (TSC) between pediatric glioma and non-neoplastic brain tissue using 23Na MRI; (2) compare tissue conspicuity of bound sodium concentration (BSC) using 23Na MRI dual echo relative to TSC imaging. Methods: TSC was measured in: (1) non-neoplastic brain tissues and (2) three types of manually segmented gliomas (diffuse intrinsic brainstem glioma (DIPG), recurrent supratentorial low-grade glioma (LGG), and high-grade glioma (HGG)). In a subset of patients, serial changes in both TSC and BSC (dual echo 23Na MRI) were assessed. Results: Twenty-six pediatric patients with gliomas (median age of 12.0 years, range 4.9–23.3 years) were scanned with 23Na MRI. DIPG treated with RT demonstrated higher TSC values than the uninvolved infratentorial tissues (p < 0.001). Recurrent supratentorial LGG and HGG exhibited higher TSC values than the uninvolved white matter (WM) and gray matter (GM) (p < 0.002 for LGG, and p < 0.02 for HGG). The dual echo 23Na MRI suppressed the sodium signal within both CSF and necrotic foci. Conclusion: Quantitative 23Na MRI of pediatric gliomas demonstrates a range of values that are higher than non-neoplastic tissues. Dual echo 23Na MRI of BCS improves tissue conspicuity relative to TSC imaging.

Background Balloon test occlusion (BTO) with adjunctive single‐photon emission computed tomography has been used to predict tolerance after permanent internal carotid artery occlusion. Anatomic characteristics of the cerebral circulation might predict BTO outcomes and identify patients susceptible to test failure. Methods We performed a single‐center retrospective analysis of patients who underwent internal carotid artery BTO from July 2013 to June 2020. Patients who passed the clinical BTO underwent single‐photon emission computed tomography imaging; technetium‐99m‐ethyl cysteinate dimer was injected intravenously after 15 to 30 minutes of occlusion and induced hypotension. The diameter of the vessels of the circle of Willis was measured angiographically. Single‐photon emission computed tomography imaging hypoperfusion severity was classified as none, mild, low intermediate, high intermediate, and severe. A threshold vessel diameter with most predicted accuracy for BTO failure was created using the Youden index. The threshold value was tested in a logistic regression for prediction of BTO failure and accuracy as represented with a receiver operator curve. Results Fifty‐seven patients underwent BTO. Neoplasia was the most common indication (n=43, 75%). Twelve (21.1%) patients failed the clinical BTO. Contralateral dominant vertebral artery (P=0.02), smaller anterior communicating artery (ACom; P=0.002), and ipsilateral posterior communicating artery (P=0.03) diameters were correlated with clinical BTO failure. Smaller ACom was most predictive with an area under the curve of 0.907. The Youden index identified an ACom diameter threshold of 1.1 mm, with a sensitivity of 91.7% and specificity of 77.8% (odds ratio, 0.026 [95% CI, 0.003–0.226]; receiver operating characteristic, 0.847) for predicting BTO failure. Patients with severe single‐photon emission computed tomography asymmetry had significantly smaller‐caliber ACom arteries (ACom median diameter, 0.95 versus 1.4 mm; P=0.0073). Conclusions Angiographic findings can be used to predict BTO results. A small ipsilateral posterior communicating artery, and more significantly, a small ACom (<1.1 mm) can be used to identify patients who are likely to fail BTO.

Tau PET tracers exhibit varying levels of specific signal and distinct off-target binding patterns that are more diverse than amyloid PET tracers. This study compared 2 frequently used tau PET tracers, F-18-flortaucipir and F-18-MK-6240, in the same subjects. Methods: F-18-flortaucipir and F-18-MK-6240 scans were collected within 2 mo in 15 elderly subjects varying in clinical diagnosis and cognition. Free-Surfer, version 5.3, was applied to 3-T MR images to segment Braak pathologic regions (I-VI) for PET analyses. Off-target binding was assessed in the choroid plexus, meninges, and striatum. SUV ratio (SUVR) outcomes were determined over 80-100 min (F-18-flortaucipir) or 70-90 min (F-18-MK-6240) normalized to cerebellar gray matter. Masked visual interpretation of images was performed by 5 raters for both the medial temporal lobe and the neocortex, and an overall (majority) rating was determined. Results: Overall visual ratings showed complete concordance between radiotracers for both the medial temporal lobe and the neocortex. SUVR outcomes were highly correlated (r(2) > 0.92; P << 0.001) for all Braak regions except Braak II. The dynamic range of SUVRs in target regions was approximately 2-fold higher for F-18-MK-6240 than for F-18-flortaucipir. Cerebellar SUVs were similar for F-18-MK-6240 and F-18-flortaucipir, suggesting that differences in SUVRs are driven by specific signals. Apparent off-target binding was observed often in the striatum and choroid plexus with F-18-flortaucipir and most often in the meninges with F-18-MK-6240. Conclusion: Both F-18-MK-6240 and F-18-flortaucipir are capable of quantifying signal in a common set of brain regions that develop tau pathology in Alzheimer disease; these tracers perform equally well in visual interpretations. Each also shows distinct patterns of apparent off-target binding. F-18-MK-6240 showed a greater dynamic range in SUVR estimates, which may be an advantage in detecting early tau pathology or in performing longitudinal studies to detect small interval changes.

Up to 30% of patients with epilepsy may not respond to antiepileptic drugs. Patients with drug-resistant epilepsy (DRE) should undergo evaluation for seizure onset zone (SOZ) localization to consider surgical treatment. Cases of drug-resistant nonlesional extratemporal lobe epilepsy (ETLE) pose the biggest challenge in localizing the SOZ and require multiple noninvasive diagnostic investigations before planning the intracranial monitoring (ICM) or direct resection. Ictal Single Photon Emission Computed Tomography (i-SPECT) is a unique functional diagnostic tool that assesses the SOZ using the localized hyperperfusion that occurs early in the seizure. Subtraction ictal SPECT coregistered to MRI (SISCOM), statistical ictal SPECT coregistered to MRI (STATISCOM), and PET interictal subtracted ictal SPECT coregistered with MRI (PISCOM) are innovative SPECT methods for the determination of the SOZ. This article comprehensively reviews SPECT and sheds light on its vital role in the presurgical evaluation of the nonlesional extratemporal DRE.

Surgery holds the best outcomes for drug-resistant epilepsy in children, making localization of a seizure focus essential. However, there is limited research on the contribution of magnetoencephalography and single-photon emission computed tomography (SPECT) to the presurgical evaluation of lesional and nonlesional pediatric patients. This study proposed to evaluate the concordance of SPECT and magnetoencephalography (MEG) to scalp electroencephalography (EEG) to determine their effective contribution to the presurgical evaluation. On review, MEG and SPECT studies for 28 drug-resistant epilepsy cases were completed at Children's Hospital of Pittsburgh from May 2012 to August 2018. Although not reaching statistical significance, MEG had increased lobar concordance with EEG compared with SPECT (68% vs 46%). MEG or SPECT results effectively provided localization data leading to 6 surgical evaluations and 3 resections with outcomes of Engel class I or II at 12 months. This study suggests MEG and SPECT provide valuable localizing information for presurgical epilepsy evaluation of children with drug-resistant epilepsy.

Background: Ictal Single Photon Emission Computed Tomography (iSPECT) is one of the established tools utilized in the presurgical evaluation of patients with drug-resistant epilepsy (DRE). Timely isotope injection for an iSPECT is critical for optimal yield but poses logistical challenges when done manually. We aim to evaluate the added value of automatic iSPECT injectors (ASIs) in overcoming such challenges. Methods: We retrospectively reviewed all cases admitted to the University of Pittsburgh Medical Center (UPMC) Epilepsy Monitoring Unit from Jan 1, 2010, through Dec 31, 2016, who underwent an iSPECT. We compared the manually injected iSPECTs with those performed with ASIs. Results: A total of 123 iSPECTs were reviewed. The manually injected iSPECT group consisted of 35 patients (median age, 35 years; and 19 males). The automatically injected iSPECT group consisted of 88 patients (median age, 36 years; and 46 males). The two groups were comparable in age, gender, epilepsy treatment, focal features on neuropsychological testing (NPT), EEG, and MRI, and temporal origin of seizures (p > 0.05). Compared to manually injected iSPECTs, automatically injected ISPECTs' median injection latency (IL) was shorter (18.5 vs. 60 s, p < 0.001); the ratio of IL/total duration of seizure was lower (0.395 vs. 0.677, p < 0.001); postictal injections were less frequent (4 (4.5 %) vs. 7 (20 %), p = 0.007); the number of isotope spills was less (zero vs. 3, p = 0.022); and successfully localizing iSPECTs were more prevalent (81.8 % vs. 62.9 %, p = 0.025), even after adjusting for focal features on NPT, EEG, and MRI, the temporal origin of seizures, and seizure duration (OR of 5.539, 95 %CI = 1.653-18.563, p = 0.006). Conclusions: Utilization of ASIs leads to a significant shortening of iSPECT IL with less postictal injections, provides a safer injection option for the EMU staff, and leads to a significant improvement in the number of successfully localizing iSPECTs.

Hybrid imaging with F-18 fludeoxyglucose positron emission tomography/magnetic resonance imaging (FDG PET/MRI) has increasing clinical applications supplementing conventional ultrasound, CT, and MRI imaging as well as hybrid PET/CT imaging in assessing cervical, endometrial, and ovarian cancer. This article summarizes the existing literature and discusses the emerging role of hybrid PET/MRI in gynecologic malignancies. Thus far, the published literature on the applications of FDG PET/MRI shows that it can have a significant impact on patient management by improving the staging of the cancers compared with PET/CT, influencing clinical decision and treatment strategy. For disease restaging, current literature indicates that PET/MRI performs equivalently to PET/CT. There appears to be a mild-moderate inverse correlation between standard-uptake-value (SUV) and apparent-diffusion-coefficient (ADC) values, which could be used to predict tumor grading and risk stratification. It remains to be seen as to whether multi-parametric PET/MRI imaging could prove valuable for prognostication and outcome. PET/MRI provides the opportunity for reduced radiation exposure, which is particularly relevant for a young female in need of multiple scans for treatment monitoring and follow-up. Fast acquisition protocols and optimized methods for attenuation correction are still evolving. Major limitations of PET/MRI remains such as suboptimal detection of small pulmonary nodules and lack of utility for radiation treatment planning, which pose an impediment in making PET/MRI a viable one-stop-shop imaging option to compete with PET/CT.

Quantitative imaging biomarkers (QIBs) provide medical image–derived intensity, texture, shape, and size features that may help characterize cancerous tumors and predict clinical outcomes. Successful clinical translation of QIBs depends on the robustness of their measurements. Biomarkers derived from positron emission tomography images are prone to measurement errors owing to differences in image processing factors such as the tumor segmentation method used to define volumes of interest over which to calculate QIBs. We illustrate a new Bayesian statistical approach to characterize the robustness of QIBs to different processing factors. Study data consist of 22 QIBs measured on 47 head and neck tumors in 10 positron emission tomography/computed tomography scans segmented manually and with semiautomated methods used by 7 institutional members of the NCI Quantitative Imaging Network. QIB performance is estimated and compared across institutions with respect to measurement errors and power to recover statistical associations with clinical outcomes. Analysis findings summarize the performance impact of different segmentation methods used by Quantitative Imaging Network members. Robustness of some advanced biomarkers was found to be similar to conventional markers, such as maximum standardized uptake value. Such similarities support current pursuits to better characterize disease and predict outcomes by developing QIBs that use more imaging information and are robust to different processing factors. Nevertheless, to ensure reproducibility of QIB measurements and measures of association with clinical outcomes, errors owing to segmentation methods need to be reduced.

Neuroimaging plays a vital role in the diagnosis and post-treatment assessment of brain tumors, aiding in treatment optimization, prognostication, and patient management. New clinical treatments have resulted in increased complexity of imaging interpretation, thus integrating complementary information from multiple imaging modalities (computed tomography, magnetic resonance imaging, and nuclear medicine) contributes to a thorough and more accurate evaluation. In review, we discuss current strategies of brain tumor imaging, specifically detailing the role of nuclear medicine single-photon emission computed tomography and positron emission tomography with utilization of both common and uncommon radiotracers in tumor grading, diagnosis, and treatment response.

We report our PET/MRI experience from a pilot study that compared the diagnostic performance of 18F-FDG PET/MRI versus PET/CT in staging of cervical cancer. Methods: Six adults with newly diagnosed cervical cancer underwent a single 18F-FDG injection with a dual-imaging protocol: standard-of-care PET/CT followed by research PET/MRI. The diagnostic interpretation and SUVmax for the 2 modalities were compared. Results: Both modalities detected all primary tumors (median size, 3.9 cm) and all 4 metastases present in 2 of the 6 patients (median size, 0.9 cm). PET/MRI provided greater diagnostic confidence than PET/CT and upstaged the disease in 4 patients. On the basis of the imaging findings alone, the additional information from PET/MRI would have led to a change in clinical management in 3 of 6 patients. The primary lesion showed a median SUV of 12.8 on PET/CT and 18.2 on PET/MRI (P = 0.03). SUVs, however, correlated strongly between the 2 modalities (ρ = 0.96, P < 0.001). Conclusion: Our pilot study supports the notion that PET/MRI has the potential to impact clinical decisions and treatment strategies in women with cervical cancer. Further studies are, however, warranted to define the value that PET/MRI adds to PET/CT.

Background Trauma-related neurodegeneration can be difficult to differentiate from multifactorial neurodegenerative syndromes, both clinically and radiographically. We have initiated a protocol for in vivo imaging of patients with suspected TBI-related neurodegeneration utilizing volumetric MRI and PET studies, including [18F]FDG indexing cerebral glucose metabolism, [11C]PiB for Aβ deposition, and [18F]AV-1451 for tau deposition. Objective To present results from a neuroimaging protocol for in vivo evaluation of TBI-related neurodegeneration in patients with early-onset cognitive decline and a history of TBI. Methods Patients were enrolled in parallel TBI studies and underwent a comprehensive neuropsychological test battery as well as an imaging protocol of volumetric MRI and PET studies. Findings from two patients were compared with two age-matched control subjects without a history of TBI. Results Both chronic TBI patients demonstrated cognitive deficits consistent with early-onset dementia on neuropsychological testing, and one patient self-reported a diagnosis of probable early-onset AD. Imaging studies demonstrated significant [18F]AV-1451 uptake in the bilateral occipital lobes, substantial [11C]PiB uptake throughout the cortex in both TBI patients, and abnormally decreased [18F]FDG uptake in the posterior temporoparietal areas of the brain. One TBI patient also had subcortical volume loss. Control subjects demonstrated no appreciable [18F]AV-1451 or [11C]PiB uptake, had normal cortical volumes, and had normal cognition profiles on neuropsychological testing. Conclusions In the two patients presented, the [11C]PiB and [18F]FDG PET scans demonstrate uptake patterns characteristic of AD. [11C]PiB PET scans showed widespread neocortical uptake with less abnormal uptake in the occipital lobes, whereas there was significant [18F]AV-1451 uptake in both occipital lobes.

INTRODUCTION: TBI (traumatic brain injury) is associated with an increased risk of late neurodegeneration in chronic TBI survivors. The underlying pathophysiology of trauma-related neurodegeneration is hypothesized to involve a tauopathy, with p-tau deposited in beta-pleated sheets. Current research focuses on identifying strategies to detect trauma-related neurodegeneration in-Vivo. [F-18]AV-1451, a tau-specific PET radiotracer, may detect hyper-phosphorylated tau deposits in living patients. METHODS: Participants with a history of TBI >6 mo prior with concern for cognitive decline with age-matched controls were recruited. Subjects were classified into three groups: few (=3 TBI exposures), intermediate (4-10 exposures), and numerous (>10 exposures). Participants underwent PET imaging with [F-18]AV-1451, and qualitative and semi-quantitative (SUVR) analyses of radiotracer retention were performed. Visual classification of tau positivity (+/−) was performed with absence of established positivity thresholds for [F-18]AV-1451 SUVR values. All subjects underwent neuropsychological evaluation, including measures of processing speed, executive function, and memory. RESULTS: Twenty-seven TBI subjects and 7 controls were enrolled. A total of 9 participants were categorized as few, 2 as intermediate, 7 as numerous. All TBI subjects demonstrated impairment on at least one neurocognitive measure, while control subjects had normal neuropsychological test results. Analysis of [F-18]AV-1451 uptake patterns demonstrated evidence of tauopathy in 3 subjects, based on visual reads. Significantly increased [F-18]AV-1451 retention was noted in occipital gray matter, posterior cingulate gyrus, and parietal cortex in these 3 tau (+) TBI subjects compared to 24 TBI subjects visually classified as tau (−) and also normal controls. CONCLUSION: Evidence of tauopathy, indicative of trauma-related neurodegeneration, was noted in 3 chronic TBI subjects, all of whom were categorized as numerous (>10) TBI exposures and cognitive deficits on neuropsychological testing. No tau PET [F-18]AV-1451 uptake was noted in control participants or in participants categorized as few or intermediate. The data represent a possible [F-18]AV-1451 PET uptake pattern associated with a clinical neurodegeneration syndrome in repetitive TBI.

A 72-year-old man with a history of T1cN0M0 prostate adenocarcinoma and rising prostate-specific antigen underwent a fluciclovine PET/CT scan that showed high uptake in several para-aortic nodes, suspicious for prostate cancer. A right upper lobe single pulmonary nodule (SPN), demonstrated only mild uptake, which raised the suspicion for a lung primary. Subsequent FDG PET/CT showed high uptake in the SPN, revealing poorly differentiated adenocarcinoma at biopsy, but with no abnormal uptake in the para-aortic nodes. This case highlights the complementary potential of fluciclovine and FDG PET in patients with a history of prostate cancer biochemical recurrence and SPN.

This multicenter study evaluated the effect of variations in arterial input function (AIF) determination on pharmacokinetic (PK) analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data using the shutter-speed model (SSM). Data acquired from eleven prostate cancer patients were shared among nine centers. Each center used a site-specific method to measure the individual AIF from each data set and submitted the results to the managing center. These AIFs, their reference tissue-adjusted variants, and a literature population-averaged AIF, were used by the managing center to perform SSM PK analysis to estimate Ktrans (volume transfer rate constant), ve (extravascular, extracellular volume fraction), kep (efflux rate constant), and τi (mean intracellular water lifetime). All other variables, including the definition of the tumor region of interest and precontrast T1 values, were kept the same to evaluate parameter variations caused by variations in only the AIF. Considerable PK parameter variations were observed with within-subject coefficient of variation (wCV) values of 0.58, 0.27, 0.42, and 0.24 for Ktrans, ve, kep, and τi, respectively, using the unadjusted AIFs. Use of the reference tissue-adjusted AIFs reduced variations in Ktrans and ve (wCV = 0.50 and 0.10, respectively), but had smaller effects on kep and τi (wCV = 0.39 and 0.22, respectively). kep is less sensitive to AIF variation than Ktrans, suggesting it may be a more robust imaging biomarker of prostate microvasculature. With low sensitivity to AIF uncertainty, the SSM-unique τi parameter may have advantages over the conventional PK parameters in a longitudinal study.