Faculty Bibliography

OBJECTIVE:To evaluate the influence of coronary artery dominance on observed coronary artery calcification burden in outpatients presenting for coronary computed tomography angiography (CCTA). METHODS:A 12-month retrospective review was performed of all CCTAs at a single institution. Coronary arterial dominance, Agatston score and presence or absence of cardiovascular risk factors including hypertension (HTN), hyperlipidemia (HLD), diabetes and smoking were recorded. Dominance groups were compared in terms of calcium score adjusted for covariates using analysis of covariance based on ranks. Only covariates observed to be significant independent predictors of the relevant outcome were included in each analysis. All statistical tests were conducted at the two-sided 5% significance level. RESULTS:1223 individuals, 618 women and 605 men were included, mean age 60 years (24-93 years). Right coronary dominance was observed in 91.7% (n = 1109), left dominance in 8% (n = 98), and codominance in 1.3% (n = 16). The distribution of patients among Agatston score severity categories significantly differed between codominant and left (p = 0.008), and codominant and right (p = 0.022) groups, with higher prevalence of either zero or severe CAC in the codominant patients. There was no significant difference in Agatston score between dominance groups. In the subset of individuals with coronary artery calcification, Agatston score was significantly higher in codominant versus left dominant patients (mean Agatston score 595 ± 520 vs. mean 289 ± 607, respectively; p = 0.049), with a trend towards higher scores in comparison to the right-dominant group (p = 0.093). Significance was not maintained upon adjustment for covariates. CONCLUSIONS:While the distribution of Agatston score severity categories differed in codominant versus right- or left-dominant patients, there was no significant difference in Agatston score based on coronary dominance pattern in our cohort. Reporting and inclusion of codominant subsets in larger investigations may elucidate whether codominant anatomy is associated with differing risk.

The aim of this study was to determine the feasibility of diffusion basis spectrum imaging in multiple sclerosis at 7 T and to investigate the pathological substrates of tissue damage in lesions and normal-appearing white matter. To this end, 43 patients with multiple sclerosis (24 relapsing-remitting, 19 progressive), and 21 healthy control subjects were enrolled. White matter lesions were classified in T1-isointense, T1-hypointense and black holes. Mean values of diffusion basis spectrum imaging metrics (fibres, restricted and non-restricted fractions, axial and radial diffusivities and fractional anisotropy) were measured from whole brain white matter lesions and from both lesions and normal appearing white matter of the corpus callosum. Significant differences were found between T1-isointense and black holes (P ranging from 0.005 to <0.001) and between lesions' centre and rim (P < 0.001) for all the metrics. When comparing the three subject groups in terms of metrics derived from corpus callosum normal appearing white matter and T2-hyperintense lesions, a significant difference was found between healthy controls and relapsing-remitting patients for all metrics except restricted fraction and fractional anisotropy; between healthy controls and progressive patients for all metrics except restricted fraction and between relapsing-remitting and progressive multiple sclerosis patients for all metrics except fibres and restricted fractions (P ranging from 0.05 to <0.001 for all). Significant associations were found between corpus callosum normal-appearing white matter fibres fraction/non-restricted fraction and the Symbol Digit Modality Test (respectively, r = 0.35, P = 0.043; r = -0.35, P = 0.046), and between black holes radial diffusivity and Expanded Disability Status Score (r = 0.59, P = 0.002). We showed the feasibility of diffusion basis spectrum imaging metrics at 7 T, confirmed the role of the derived metrics in the characterization of lesions and normal appearing white matter tissue in different stages of the disease and demonstrated their clinical relevance. Thus, suggesting that diffusion basis spectrum imaging is a promising tool to investigate multiple sclerosis pathophysiology, monitor disease progression and treatment response.

BACKGROUND:Emerging data suggest screening mammography may be effective in detecting breast cancer early in high-risk men. We evaluated current screening recommendations as a risk management strategy in men at elevated risk for breast cancer. PATIENTS AND METHODS/METHODS:This institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study reviewed consecutive men who underwent genetic counseling and multigene panel testing (MGPT) for breast cancer risk assessment at our institution between 2012 and 2018. Patient risk factors, test indications, and MGPT outcomes were recorded, then correlated with screening recommendations by either clinical breast examination or screening mammography. Recommendation consistency among practitioners was evaluated. Patient adherence to screening mammography (defined as undergoing screening mammography as recommended) was assessed. Statistical analysis was performed at the 2-sided 5% significance level. RESULTS:A total of 414 asymptomatic men underwent both genetic counseling and MGPT (mean age, 47 years; range, 18-91 years) for breast cancer risk assessment. Of this group, 18 (4.3%) of 414 had a personal history of breast cancer, and 159 (38.4%) of 414 had a family history of breast cancer before MGPT. Among 112 men with positive MGPT results, BRCA1/2 mutations were the most common (56.3%, 63/112). Most BRCA mutation carriers (80.9%, 51/63) were recommended clinical breast examination only. Only 5.9% (2/34) BRCA2 and 10.3% (3/29) BRCA1 carriers were recommended screening mammograms (7.9%, 5/63 of all BRCA carriers). Among men with a personal history of breast cancer, only 9 (50%) of 18 were recommended screening mammograms. Overall adherence to screening mammogram in men was 71.4% (10/14), which ultimately yielded two cancers. Breast cancer screening recommendations varied widely among practitioners, with some recommending clinical breast examination only, and others also recommending mammography. CONCLUSION/CONCLUSIONS:Men who are found to be at an elevated risk for breast cancer after undergoing genetic counseling and testing currently receive relatively inconsistent screening recommendations.

The pathological cascade of tissue damage in mild traumatic brain injury is set forth by a perturbation in ionic homeostasis. However, whether this class of injury can be detected in vivo and serve as a surrogate marker of clinical outcome is unknown. We employ sodium MRI to test the hypotheses that regional and global total sodium concentrations: (i) are higher in patients than in controls and (ii) correlate with clinical presentation and neuropsychological function. Given the novelty of sodium imaging in traumatic brain injury, effect sizes from (i), and correlation types and strength from (ii), were compared to those obtained using standard diffusion imaging metrics. Twenty-seven patients (20 female, age 35.9 ± 12.2 years) within 2 months after injury and 19 controls were scanned with proton and sodium MRI at 3 Tesla. Total sodium concentration, fractional anisotropy and apparent diffusion coefficient were obtained with voxel averaging across 12 grey and white matter regions. Linear regression was used to obtain global grey and white matter total sodium concentrations. Patient outcome was assessed with global functioning, symptom profiles and neuropsychological function assessments. In the regional analysis, there were no statistically significant differences between patients and controls in apparent diffusion coefficient, while differences in sodium concentration and fractional anisotropy were found only in single regions. However, for each of the 12 regions, sodium concentration effect sizes were uni-directional, due to lower mean sodium concentration in patients compared to controls. Consequently, linear regression analysis found statistically significant lower global grey and white matter sodium concentrations in patients compared to controls. The strongest correlation with outcome was between global grey matter sodium concentration and the composite z-score from the neuropsychological testing. In conclusion, both sodium concentration and diffusion showed poor utility in differentiating patients from controls, and weak correlations with clinical presentation, when using a region-based approach. In contrast, sodium linear regression, capitalizing on partial volume correction and high sensitivity to global changes, revealed high effect sizes and associations with patient outcome. This suggests that well-recognized sodium imbalances in traumatic brain injury are (i) detectable non-invasively; (ii) non-focal; (iii) occur even when the antecedent injury is clinically mild. Finally, in contrast to our principle hypothesis, patients' sodium concentrations were lower than controls, indicating that the biological effect of traumatic brain injury on the sodium homeostasis may differ from that in other neurological disorders. Note: This figure has been annotated.

Myelin abnormalities have been reported in schizophrenia spectrum disorders (SSD) in white matter. However, in vivo examinations of cortical myeloarchitecture in SSD, especially those using quantitative measures, are limited. Here, we employed macromolecular proton fraction (MPF) obtained from quantitative magnetization transfer imaging to characterize intracortical myelin organization in 30 SSD patients versus 34 healthy control (HC) participants. We constructed cortical myelin profiles by extracting MPF values at various cortical depths and quantified their shape using a nonlinearity index (NLI). To delineate the association of illness duration with myelin changes, SSD patients were further divided into 3 duration groups. Between-group comparisons revealed reduced NLI in the SSD group with the longest illness duration (>5.5 years) compared with HC predominantly in bilateral prefrontal areas. Within the SSD group, cortical NLI decreased with disease duration and was positively associated with a measure of spatial working memory capacity as well as with cortical thickness (CT). Layer-specific analyses suggested that NLI decreases in the long-duration SSD group may arise in part from significantly increased MPF values in the midcortical layers. The current study reveals cortical myelin profile changes in SSD with illness progression, which may reflect an abnormal compensatory mechanism of the disorder.

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

ABSTRACT/UNASSIGNED:This study aimed to evaluate the effect of an artificial intelligence (AI) support system on breast ultrasound diagnostic accuracy.In this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved retrospective study, 200 lesions (155 benign, 45 malignant) were randomly selected from consecutive ultrasound-guided biopsies (June 2017-January 2019). Two readers, blinded to clinical history and pathology, evaluated lesions with and without an Food and Drug Administration-approved AI software. Lesion features, Breast Imaging Reporting and Data System (BI-RADS) rating (1-5), reader confidence level (1-5), and AI BI-RADS equivalent (1-5) were recorded. Statistical analysis was performed for diagnostic accuracy, negative predictive value, positive predictive value (PPV), sensitivity, and specificity of reader versus AI BI-RADS. Generalized estimating equation analysis was used for reader versus AI accuracy regarding lesion features and AI impact on low-confidence score lesions. Artificial intelligence effect on false-positive biopsy rate was determined. Statistical tests were conducted at a 2-sided 5% significance level.There was no significant difference in accuracy (73 vs 69.8%), negative predictive value (100% vs 98.5%), PPV (45.5 vs 42.4%), sensitivity (100% vs 96.7%), and specificity (65.2 vs 61.9; P = 0.118-0.409) for AI versus pooled reader assessment. Artificial intelligence was more accurate than readers for irregular shape (74.1% vs 57.4%, P = 0.002) and less accurate for round shape (26.5% vs 50.0%, P = 0.049). Artificial intelligence improved diagnostic accuracy for reader-rated low-confidence lesions with increased PPV (24.7% AI vs 19.3%, P = 0.004) and specificity (57.8% vs 44.6%, P = 0.008).Artificial intelligence decision support aid may help improve sonographic diagnostic accuracy, particularly in cases with low reader confidence, thereby decreasing false-positives.

PURPOSE/OBJECTIVE:To assess the utility of a 2D dynamic HASTE sequence in assessment of cervical spine flexion-extension, specifically (1) comparing dynamic spondylolisthesis to radiographs and (2) assessing dynamic contact upon or deformity of the cord. METHODS:Patients with a dynamic flexion-extension sagittal 2D HASTE sequence in addition to routine cervical spine sequences were identified. Static and dynamic listhesis was first determined on flexion-extension radiographs reviewed in consensus. Blinded assessment of the dynamic HASTE sequence was independently performed by 2 radiologists for (1) listhesis and translation during flexion-extension and (2) dynamic spinal cord impingement (cord contact or deformity between neutral, flexion and extension). RESULTS:32 scans in 32 patients (9 males, 23 females) met inclusion criteria acquired on 1.5 T (n = 15) and 3 T (n = 17) scanners. The mean acquisition time was 51.8 s (range 20-95 seconds). Dynamic translation was seen in 14 patients on flexion-extension radiographs compared to 12 (reader 1) and 13 (reader 2) patients on HASTE, with 90.6 % agreement (K = 0.83; p = 0.789). In all cases dynamic listhesis was ≤3 mm translation with one patient showing dynamic listhesis in the range 4-6 mm. Four cases (13 %) demonstrated deformity of the cord between flexion-extension, not present in the neutral position. For cord impingement there was strong inter-reader agreement (K = 0.93) and the paired sample Wilcoxon signed rank test found no significant difference between the impingement scores of the two readers (p = 0.787). CONCLUSIONS:A sagittal dynamic flexion-extension HASTE sequence provides a rapid addition to standard MRI cervical spine protocols, which may useful for assessment of dynamic spondylolisthesis and cord deformity.

OBJECTIVES/OBJECTIVE:The primary objective was to compare the performance of 3 different abbreviated MRI (AMRI) sets extracted from a complete gadoxetate-enhanced MRI obtained for hepatocellular carcinoma (HCC) screening. Secondary objective was to perform a preliminary cost-effectiveness analysis, comparing each AMRI set to published ultrasound performance for HCC screening in the USA. METHODS:This retrospective study included 237 consecutive patients (M/F, 146/91; mean age, 58 years) with chronic liver disease who underwent a complete gadoxetate-enhanced MRI for HCC screening in 2017 in a single institution. Two radiologists independently reviewed 3 AMRI sets extracted from the complete exam: non-contrast (NC-AMRI: T2-weighted imaging (T2wi)+diffusion-weighted imaging (DWI)), dynamic-AMRI (Dyn-AMRI: T2wi+DWI+dynamic T1wi), and hepatobiliary phase AMRI (HBP-AMRI: T2wi+DWI+T1wi during the HBP). Each patient was classified as HCC-positive/HCC-negative based on the reference standard, which consisted in all available patient data. Diagnostic performance for HCC detection was compared between sets. Estimated set characteristics, including historical ultrasound data, were incorporated into a microsimulation model for cost-effectiveness analysis. RESULTS:The reference standard identified 13/237 patients with HCC (prevalence, 5.5%; mean size, 33.7 ± 30 mm). Pooled sensitivities were 61.5% for NC-AMRI (95% confidence intervals, 34.4-83%), 84.6% for Dyn-AMRI (60.8-95.1%), and 80.8% for HBP-AMRI (53.6-93.9%), without difference between sets (p range, 0.06-0.16). Pooled specificities were 95.5% (92.4-97.4%), 99.8% (98.4-100%), and 94.9% (91.6-96.9%), respectively, with a significant difference between Dyn-AMRI and the other sets (p < 0.01). All AMRI methods were effective compared with ultrasound, with life-year gain of 3-12 months against incremental costs of US$ < 12,000. CONCLUSIONS:NC-AMRI has limited sensitivity for HCC detection, while HBP-AMRI and Dyn-AMRI showed excellent sensitivity and specificity, the latter being slightly higher for Dyn-AMRI. Cost-effectiveness estimates showed that AMRI is effective compared with ultrasound. KEY POINTS/CONCLUSIONS:• Comparison of different abbreviated MRI (AMRI) sets reconstructed from a complete gadoxetate MRI demonstrated that non-contrast AMRI has low sensitivity (61.5%) compared with contrast-enhanced AMRI (80.8% for hepatobiliary phase AMRI and 84.6% for dynamic AMRI), with all sets having high specificity. • Non-contrast and hepatobiliary phase AMRI can be performed in less than 14 min (including set-up time), while dynamic AMRI can be performed in less than 17 min. • All AMRI sets were cost-effective for HCC screening in at-risk population in comparison with ultrasound.

We characterize the whole-brain N-acetyl-aspartate (WBNAA) and brain tissue fractions across the adult lifespan and test the hypothesis that, despite age-related atrophy, neuronal integrity (reflected by WBNAA) is preserved in normal aging. Two-hundred-and-seven participants: 133 cognitively intact older adults (73.6 ± 7.4 mean ± standard deviation, range: 60-90 year old) and 84 young (37.9 ± 11, range: 21-59 year old) were scanned with proton magnetic resonance spectroscopy and T₁-weighted MRI. Their WBNAA, fractional brain parenchyma, and gray and white matter volumes (fBPV, fGM, and fWM) were compared and modeled as functions of age and sex. Compared with young, older-adults' WBNAA was lower by ~35%, and fBPV, fGM and fWM were lower by ~10%. Linear regressions found 0.5%/year WBNAA and 0.2%/year fBPV and fGM declines, whereas fWM rose to age ~40 years, and declined thereafter. fBPV and fGM were 1.8% and 4% higher in women, with no sex decline rates difference. We conclude that contrary to our hypothesis, atrophy was accompanied by WBNAA decline. Across the entire age range, women's brains showed less atrophy than men's. Formulas to estimate WBNAA and brain tissue fractions in healthy adults are provided to help differentiate normal from abnormal aging.