Faculty Bibliography

RATIONALE AND OBJECTIVES/OBJECTIVE:Periventricular and deep white matter hyperintensities (WMHs) in the elderly have been reported with distinctive roles in the progression of cognitive decline and dementia. However, the definition of these two subregions of WMHs is arbitrary and varies across studies. Here, we evaluate three partition methods for WMH subregions, including two widely used conventional methods (CV & D10) and one novel method based on bilateral distance (BD). MATERIALS AND METHODS/METHODS:The three partition methods were assessed on the MRI scans of 60 subjects, with 20 normal control, 20 mild cognitive impairment, and 20 Alzheimer's disease (AD). Resulting WMH subregional volumes were (1) compared among different partition methods and subject groups, and (2) tested for clinical associations with cognition and dementia. Inter-rater, intrarater, and interscan reproducibility of WMHs volumes were tested on 12 randomly selected subjects from the 60. RESULTS:For all three partition methods, increased periventricular WMHs were found for AD subjects over normal control. For BD and D10, but not CV method, increased Periventricular WMHs were found for AD subjects over mild cognitive impairment. Significant correlations were found between PVWMHs and Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating scores. Furthermore, PVWMHs under BD partition showed higher correlations than D10 and CV. High intrarater and interscan reproducibility (ICCA = 0.998 and 0.992 correspondingly) and substantial inter-rater reproducibility (ICCA = 0.886) were detected. CONCLUSION/CONCLUSIONS:Different WMH partition methods showed comparable diagnostic abilities. The proposed BD method showed advantages in quantifying PVWMH over conventional CV and D10 methods, in terms of higher consistency, larger contrast, and higher diagnosis accuracy. Furthermore, the PVWMH under BD partition showed stronger clinical correlations than conventional methods.

PURPOSE/OBJECTIVE:To assess prognostic value of body composition parameters measured at CT to predict risk of hospitalization in patients with COVID-19 infection. METHODS:177 patients with SARS-CoV-2 infection and with abdominopelvic CT were included in this retrospective IRB approved two-institution study. Patients were stratified based on disease severity as outpatients (no hospital admission) and patients who were hospitalized (inpatients). Two readers blinded to the clinical outcome segmented axial CT images at the L3 vertebral body level for visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), muscle adipose tissue (MAT), muscle mass (MM). VAT to total adipose tissue ratio (VAT/TAT), MAT/MM ratio, and muscle index (MI) at L3 were computed. These measures, along with detailed clinical risk factors, were compared in patients stratified by severity. Various logistic regression clinical and clinical + imaging models were compared to discriminate inpatients from outpatients. RESULTS:There were 76 outpatients (43%) and 101 inpatients. Male gender (p = 0.013), age (p = 0.0003), hypertension (p = 0.0003), diabetes (p = 0.0001), history of cardiac disease (p = 0.007), VAT/TAT (p < 0.0001), and MAT/MM (p < 0.0001), but not BMI, were associated with hospitalization. A clinical model (age, gender, BMI) had AUC of 0.70. Addition of VAT/TAT to the clinical model improved the AUC to 0.73. Optimal model that included gender, BMI, race (Black), MI, VAT/TAT, as well as interaction between gender and VAT/TAT and gender and MAT/MM demonstrated the highest AUC of 0.83. CONCLUSION/CONCLUSIONS:MAT/MM and VAT/TAT provides important prognostic information in predicting patients with COVID-19 who are likely to require hospitalization.

Deep and periventricular white matter hyperintensities (dWMH/pvWMH) are bright appearing white matter tissue lesions in T2-weighted fluid attenuated inversion recovery magnetic resonance images and are frequent observations in the aging human brain. While early stages of these white matter lesions are only weakly associated with cognitive impairment, their progressive growth is a strong indicator for long-term functional decline. DWMHs are typically associated with vascular degeneration in diffuse white matter locations; for pvWMHs, however, no unifying theory exists to explain their consistent onset around the horns of the lateral ventricles. We use patient imaging data to create anatomically accurate finite element models of the lateral ventricles, white and gray matter, and cerebrospinal fluid, as well as to reconstruct their WMH volumes. We simulated the mechanical loading of the ependymal cells forming the primary brain-fluid interface, the ventricular wall, and its surrounding tissues at peak ventricular pressure during the hemodynamic cycle. We observe that both the maximum principal tissue strain and the largest ependymal cell stretch consistently localize in the anterior and posterior horns. Our simulations show that ependymal cells experience a loading state that causes the ventricular wall to be stretched thin. Moreover, we show that maximum wall loading coincides with the pvWMH locations observed in our patient scans. These results warrant further analysis of white matter pathology in the periventricular zone that includes a mechanics-driven deterioration model for the ventricular wall.

PURPOSE/OBJECTIVE:To assess the ability to discriminate oncocytoma from RCC based on a model using whole tumor ADC histogram parameters with additional use of tumor volume and patient characteristics. METHOD/METHODS:In this prospective study, 39 patients (mean age 65 years, range 28-79; 9/39 (23%) female) with 39 renal tumors (32/39 (82%) RCC and 7/39 (18%) oncocytoma) underwent multiparametric MRI between November 2014 and June 2018. Two regions of interest (ROIs) were drawn to cover both the entire tumor volume and a part of healthy renal cortex. ROI ADC maps were calculated using a mono-exponential model and ADC histogram distribution parameters were calculated. A logistic regression model was created using ADC histogram parameters, radiographic and patient characteristics that were significantly different between oncocytoma and RCC. A ROC curve of the model was constructed and the AUC, sensitivity and specificity were calculated. Furthermore, differences in intra-patient ADC histogram parameters between renal tumor and healthy cortex were calculated. A separate ROC curve was constructed to differentiate oncocytoma from RCC using statistically significant intra-patient parameter differences. RESULTS:ADC standard deviation (p = 0.008), entropy (p = 0.010), tumor volume (p = 0.012), and patient sex (p = 0.018) were significantly different between RCC and oncocytoma. The regression model of these parameters combined had an ROC-AUC of 0.91 with a sensitivity of 86% and specificity of 84%. Intra-patient difference in ADC 25th percentile (p < 0.01) and entropy (p = 0.030) combined had a ROC-AUC of 0.86 with a sensitivity and specificity of 86%, and 81%, respectively. CONCLUSION/CONCLUSIONS:A model combining ADC standard deviation and entropy with tumor volume and patient sex has the highest diagnostic value for discrimination of oncocytoma. Although less accurate, intra-patient difference in ADC 25th percentile and entropy between renal tumor and healthy cortex can also be used. Although the results of this preliminary study do not yet justify clinical use of the model, it does stimulate further research using whole tumor ADC histogram parameters.

Background: Multiple commercial and open-source software applications are available for texture analysis. Nonstandard techniques can cause undesirable variability that impedes result reproducibility and limits clinical utility. Objective: The purpose of this study is to measure agreement of texture metrics extracted by 6 software packages. Methods: This retrospective study included 40 renal cell carcinomas with contrast-enhanced CT from The Cancer Genome Atlas and Imaging Archive. Images were analyzed by 7 readers at 6 sites. Each reader used 1 of 6 software packages to extract commonly studied texture features. Inter and intra-reader agreement for segmentation was assessed with intra-class correlation coefficients. First-order (available in 6 packages) and second-order (available in 3 packages) texture features were compared between software pairs using Pearson correlation. Results: Inter- and intra-reader agreement was excellent (ICC 0.93-1). First-order feature correlations were strong (r>0.8, p<0.001) between 75% (21/28) of software pairs for mean and standard deviation, 48% (10/21) for entropy, 29% (8/28) for skewness, and 25% (7/28) for kurtosis. Of 15 second-order features, only co-occurrence matrix correlation, grey-level non-uniformity, and run-length non-uniformity showed strong correlation between software packages (0.90-1, p<0.001). Conclusion: Variability in first and second order texture features was common across software configurations and produced inconsistent results. Standardized algorithms and reporting methods are needed before texture data can be reliably used for clinical applications. Clinical Impact: It is important to be aware of variability related to texture software processing and configuration when reporting and comparing outputs.

PURPOSE/OBJECTIVE:To assess visceral (VAT), subcutaneous (SAT), and total adipose tissue (TAT) estimates at abdominopelvic CT in COVID-19 patients with different severity, and analyze Body Mass Index (BMI) and CT estimates of fat content in patients requiring hospitalization. METHODS:to discriminate hospitalized patients from outpatients. RESULTS:in hospitalized patients compared to the outpatients (all p < 0.05). Area under the curve (AUC) of the clinical + CT model was higher compared to the clinical model (AUC 0.847 versus 0.750) for identifying patients requiring hospitalization. CONCLUSION/CONCLUSIONS:to the clinical model improved AUC in discriminating hospitalized from outpatients in this preliminary study.

BACKGROUND AND PURPOSE/OBJECTIVE:Previous hippocampal proton MR spectroscopic imaging distinguished patients with schizophrenia from controls by elevated Cr levels and significantly more variable NAA and Cho concentrations. This goal of this study was to ascertain whether this metabolic variability is associated with clinical features of the syndrome, possibly reflecting heterogeneous hippocampal pathologies and perhaps variability in its "positive" (psychotic) and "negative" (social and emotional deficits) symptoms. MATERIALS AND METHODS/METHODS:, we examined the association of NAA and Cho levels with research diagnostic interviews and clinical symptom ratings of the patients. Metabolite concentrations were previously obtained with 3D proton MR spectroscopic imaging at 3T, a technique that facilitates complete coverage of this small, irregularly shaped, bilateral, temporal lobe structure. RESULTS: ≥  .055). CONCLUSIONS:These preliminary findings suggest that NAA and Cho variations reflect different pathophysiologic processes, consistent with microgliosis/astrogliosis and/or lower vitality (reduced NAA) and demyelination (elevated Cho). In particular, the active state-related symptoms, including psychosis and mania, were associated with demyelination. Consequently, their deviations from the means of healthy controls may be a marker that may benefit precision medicine in selection and monitoring of schizophrenia treatment.

Background: Despite studies suggesting that blacks may be at greater risk of developing AD, there have been few studies investigating health disparities, and blacks have been underrepresented in many prominent AD biomarker studies and clinical trials. The current ATN biomarker classification system may not fully account for health disparities and can't explain the increased prevalence among blacks for both AD and AD vascular risks of diabetes and hypertension when compared to whites. Research on cognitive aging has traditionally focused on how decline in various cortical and hippocampal (Hip) regions influences cognition. However, tau pathology emerges decades before amyloid pathology, appearing first in the brainstem (BS); particularly in the locus coeruleus (LC), the source of brain's norepinephrine (NE). Our decade-long studies in humans using a norepinephrine transporter (NET)-selective radiotracer ([11C]MRB) have demonstrated a special vulnerability of LC to aging and stress.
Method(s): Co-registration of PET (dynamic [11C]MRB), MRI and the FreeSurfer (FS) atlas images of each individual was used to generate regional time-activity curves using Firevoxel. Binding potential (BPND) values were determined using MRTM2 with occipital as the reference region. Annual percent change (APC) of BPND was calculated based on linear regression (APC = 100 x (em-1), m: slope) and effects of age, gender and ethnicity on tracer binding were evaluated.
Result(s): For all HC (N=31), with both genders and all races included, age-sensitive decline of NET availability was observed; e.g., 0.3-0.5%/yr for Hip, BS and olfactory. However, our data reveals that the decline rate of NET is much faster among blacks starting in the mid-30s, particularly in black males; e.g., 2-3%/yr vs. 0.14-0.23%/yr in thalamus and brainstem for black males vs. white males (p < 0.00001).
Conclusion(s): In addition to our previously determined age effect on MRB-NET binding, this report further reveals the role of ethnicity effects on NET availability. Our study showed that a faster decline of LC-NE function occurs in blacks, possibly caused by cumulative stress to socioeconomic disadvantage and racial discrimination and may be responsible for the different disease expression among blacks. Thus, NET availability imaging represents a novel biomarker approach to racial-dependent strategies for diagnosis and assessment of therapeutic interventions