Faculty Bibliography

We hypothesize that normal aging implies neuronal durability, reflected by age-independent concentrations of their marker-the amino acid derivative N-acetylaspartate (NAA). To test this, we obtained the whole-brain and whole-head N-acetylaspartate concentrations (WBNAA and WHNAA) with proton magnetic resonance (MR) spectroscopy; and the fractional brain parenchyma volume (fBPV)-a metric of atrophy, by segmenting the magnetic resonance image (MRI) from 42 (18 male) healthy young (31.9 +/- 5.8 years old) and 100 (64 male, 72.6 +/- 7.3 years old) cognitively normal elderly. The 12.8 +/- 1.9 mM WBNAA of the young was not significantly different from the 13.1 +/- 3.1 mM in the elderly (p > 0.05). In contrast, both fBPV (87.3 +/- 4.7% vs. 74.8 +/- 4.8%) and WHNAA (11.1 +/- 1.7 mM vs. 9.8 +/- 2.4 mM) were significantly higher in the young (approximately 14%; p < 0.0001 for both). The similarity in mean WBNAA between 2 cohorts 4 decades of normal aging apart suggests that neuronal integrity is maintained across the lifespan. Clinically, WBNAA could be used as a marker for normal (hence, also abnormal) brain aging. In contrast, WHNAA and fBPV seem age-related suggesting that brain atrophy may occur without compromising the remaining tissue.

Purpose:To assess the reproducibility and the distribution of intravoxel incoherent motion (IVIM) and diffusion-tensor (DT) imaging parameters in healthy renal cortex and medulla at baseline and after hydration or furosemide challenges.Materials and Methods:Using an institutional review board-approved HIPAA-compliant protocol with written informed consent, IVIM and DT imaging were performed at 3 T in 10 volunteers before and after water loading or furosemide administration. IVIM (apparent diffusion coefficient [ADC], tissue diffusivity [D(t)], perfusion fraction [f(p)], pseudodiffusivity [D(p)]) and DT (mean diffusivity [MD], fractional anisotropy [FA], eigenvalues [lambda(i)]) imaging parameters and urine output from serial bladder volumes were calculated. (a) Reproducibility was quantified with coefficient of variation, intraclass correlation coefficient, and Bland-Altman limits of agreement; (b) contrast and challenge response were quantified with analysis of variance; and (c) Pearson correlations were quantified with urine output.Results:Good reproducibility was found for ADC, D(t), MD, FA, and lambda(i) (average coefficient of variation, 3.7% [cortex] and 5.0% [medulla]), and moderate reproducibility was found for D(p), f(p), and f(p) . D(p) (average coefficient of variation, 18.7% [cortex] and 25.9% [medulla]). Baseline cortical diffusivities significantly exceeded medullary values except D(p), for which medullary values significantly exceeded cortical values, and lambda(1,) which showed no contrast. ADC, D(t), MD, and lambda(i) increased significantly for both challenges. Medullary diffusivity increases were dominated by transverse diffusion (1.72 +/- 0.09 [baseline] to 1.79 +/- 0.10 [hydration] mum(2)/msec, P = .0059; or 1.86 +/- 0.07 [furosemide] mum(2)/msec, P = .0094). Urine output correlated with cortical ADC with furosemide (r = 0.7, P = .034) and with medullary lambda(1) (r = 0.83, P = .0418), lambda(2) (r = 0.85, P = .0301), and MD (r = 0.82, P = .045) with hydration.Conclusion:Diffusion MR metrics are sensitive to flow changes in kidney induced by diuretic challenges. The results of this study suggest that vascular flow, tubular dilation, water reabsorption, and intratubular flow all play important roles in diffusion-weighted imaging contrast.(c) RSNA, 2012.

Purpose: To assess the feasibility of diffusional kurtosis (DK) imaging for distinguishing benign from malignant regions, as well as low- from high-grade malignant regions, within the peripheral zone (PZ) of the prostate in comparison with standard diffusion-weighted (DW) imaging. Materials and Methods: The institutional review board approved this retrospective HIPAA-compliant study and waived informed consent. Forty-seven patients with prostate cancer underwent 3-T magnetic resonance imaging by using a pelvic phased-array coil and DW imaging (maximum b value, 2000 sec/mm(2)). Parametric maps were obtained for apparent diffusion coefficient (ADC); the metric DK (K), which represents non-Gaussian diffusion behavior; and corrected diffusion (D) that accounts for this non-Gaussianity. Two radiologists reviewed these maps and measured ADC, D, and K in sextants positive for cancer at biopsy. Data were analyzed by using mixed-model analysis of variance and receiver operating characteristic curves. Results: Seventy sextants exhibited a Gleason score of 6; 51 exhibited a Gleason score of 7 or 8. K was significantly greater in cancerous sextants than in benign PZ (0.96 ± 0.24 vs 0.57 ± 0.07, P < .001), as well as in cancerous sextants with higher rather than lower Gleason score (1.05 ± 0.26 vs 0.89 ± 0.20, P < .001). K showed significantly greater sensitivity for differentiating cancerous sextants from benign PZ than ADC or D (93.3% vs 78.5% and 83.5%, respectively; P < .001), with equal specificity (95.7%, P > .99). K exhibited significantly greater sensitivity for differentiating sextants with low- and high-grade cancer than ADC or D (68.6% vs 51.0% and 49.0%, respectively; P ≤ .004) but with decreased specificity (70.0% vs 81.4% and 82.9%, respectively; P ≤ .023). K had significantly greater area under the curve for differentiating sextants with low- and high-grade cancer than ADC (0.70 vs 0.62, P = .010). Relative contrast between cancerous sextants and benign PZ was significantly greater for D or K than ADC (0.25 ± 0.14 and 0.24 ± 0.13, respectively, vs 0.18 ± 0.10; P < .001). Conclusion: Preliminary findings suggest increased value for DK imaging compared with standard DW imaging in prostate cancer assessment. Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112290/-/DC1

OBJECTIVES: To test the hypotheses that 1) patients with relapsing-remitting multiple sclerosis (RR-MS) exhibit a quantifiable decline in their whole-brain concentration of the neural marker N-acetyl-l-aspartate (WBNAA), that is 2) more sensitive than clinical changes and 3) may provide a practical outcome measure for proof-of-concept and larger phase III clinical trials. METHODS: Nineteen patients (5 men and 14 women) with clinically definite RR-MS, who were 33 +/- 5 years old (mean +/- SD), had a disease duration of 47 +/- 28 months, and had a median Expanded Disability Status Scale (EDSS) score of 1.0 (range 0-5.5), underwent MRI and proton magnetic resonance spectroscopy ((1)H-MRS) semiannually for 2 years (5 time points). Eight matched control subjects underwent the protocol annually (3 time points). Their global N-acetyl-l-aspartate (1)H-MRS signal was converted into absolute amounts by phantom replacement and into WBNAA by dividing with the brain parenchymal volume, V(B), from MRI segmentation. RESULTS: The baseline WBNAA of the patients (10.5 +/- 1.7 mM) was significantly lower than that of the controls (12.3 +/- 1.3 mM; p < 0.002) and declined significantly (5%/year, p < 0.002) vs that for the controls who did not show a decline (0.4%/year, p > 0.7). Likewise, V(B) values of the patients also declined significantly (0.5%/year, p < 0.0001), whereas those of the controls did not (0.2%/year, p = 0.08). The mean EDSS score of the patients increased insignificantly from 1.0 to 1.5 (range 0-6.0) and did not correlate with V(B) or WBNAA. CONCLUSIONS: WBNAA of patients with RR-MS declined significantly at both the group and individual levels over a 2-year time period common in clinical trials. Because of the small sample sizes required to establish power, WBNAA can be incorporated into future studies.

Introduction: Spinal cord stimulation (SCS) has been shown to modulate atrial electrophysiology and confer protection against ischemia and ventricular arrhythmias in animal models. We hypothesized that SCS would reduce the susceptibility to tachypacing (TP) induced atrial fibrillation (AF). Methods: In 21 canines, an upperthoracicSCS system (EonC Model 3688, Octrode Model 3186, St. Jude Medical, Piano TX) and custom cardiac pacing system (PM, Model 5386 or 2215-36, St. Jude Medical, Sylmar CA) were implanted. Atrial effective refractory periods (ERPs) in the high right atrium (RA) and distal coronary sinus (LA) were measured at baseline and after 15 min of SCS, after which AV nodal ablation was performed. Following recovery in a subset of canines, PM was turned on to create TP induced AF by alternately delivering TP and searching for AF. TP was interrupted by detection of AF and resumed after return to sinus rhythm. Upon initiation of TP, canines were randomized to no SCS therapy (CTL, n=6) or intermittent SCS therapy (SCS-ON, n=4) and followed for 15 weeks. AF burden, defined as the percent of time in AF relative to the total sense time, and AF inducibility, defined as the percent of TP periods resulting in AF induction, were monitored weekly. Data are presented as mean +/- standard error. Results: ERPs were significantly longer after SCS compared to baseline, byan average of21 +/-14ms (p=0.001) in LA and 29+/-12ms (p=0.002) in RA. The AF burden was significantly decreased by 34 percentage points at week 15in SCS-ON compared to CTL (56 +/- 21% vs 90 +/- 12%, p<0.05). AF inducibility was significantly reduced by 60 percentage points at week 15 in SCS-ON compared to CTL (32 +/- 10% vs 91 +/- 6%, p<0.05). Conclusions: SCS prolonged atrial ERPs and reduced AF burden and inducibility in a canine atrial TP induced AF model. These data suggest that SCS therapy may represent a treatment option for AF

Adult hypothalamic neurogenesis has recently been reported, but the cell of origin and the function of these newborn neurons are unknown. Using genetic fate mapping, we found that median eminence tanycytes generate newborn neurons. Blocking this neurogenesis altered the weight and metabolic activity of adult mice. These findings reveal a previously unreported neurogenic niche in the mammalian hypothalamus with important implications for metabolism.

The purposes of this study were to determine the occurrence rate for preoperative breast pain; describe the characteristics of this pain; evaluate for differences in demographic and clinical characteristics; and evaluate for variations in pro- and anti-inflammatory cytokine genes between women who did and did not report pain. Patients (n = 398) were recruited prior to surgery and completed self-report questionnaires on a number of pain characteristics. Genotyping was done using a custom genotyping array. Women (28.2%) who reported breast pain were significantly younger (P < .001); more likely to be nonwhite (P = .032); reported significantly lower Karnofsky Performance Status scores (P = .008); were less likely to be postmenopausal (P = .012); and had undergone significantly more biopsies (P = .006). Carriers of the minor allele for a single nucleotide polymorphism in interleukin (IL)1-receptor 1 (IL1R1) (rs2110726) were less likely to report breast pain prior to surgery (P = .007). Carriers of the minor allele for a single nucleotide polymorphism in IL13 (rs1295686) were more likely to report breast pain prior to surgery (P = .019). Findings suggest that breast pain occurs in over a quarter of women who are about to undergo breast cancer surgery. Based on phenotypic and genotypic characteristics found, inflammatory mechanisms contribute to preoperative breast pain. PERSPECTIVE: In women with breast cancer, preoperative pain may be associated with increases in inflammatory responses associated with an increased number of biopsies. In addition, differences in cytokine genes may contribute to this preoperative breast pain.

Abstract Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High = A, Moderate = B, Low = C, Very Low = D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1-9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic.