Faculty Bibliography

We describe results from a survey designed to assess patterns of communication within families shortly after an individual receives results of BRCA1 and BRCA2 mutation carrier status. Shortly after disclosure of BRCA1 and BRCA2 genetic test results, the proband was contacted by phone to administer the post disclosure survey. Questions asked included whether they had shared their results with their siblings or adult children, if there were difficulties in communicating the test results, and if there was any distress associated with the sharing of results. A total of 162 women who have received results from BRCA1 and BRCA2 genetic testing participated in the survey. The probands shared their results more often with their female than their male relatives (P < 0.001). Probands who had tested positive for a mutation in the BRCA1 or BRCA2 gene shared their results more often with their relatives than did probands who were not carriers (P = 0.002). Probands reported more often that their siblings rather than their adult children had difficulties understanding the results (P = 0.001). The probands who were carriers more often reported having difficulties explaining their results to their relatives (P < 0.001) and their relatives were upset on hearing the result more often than were the relatives of probands who were not carriers (P < 0.001). The probands who were carriers reported more often that they were upset explaining their results to their relatives than did the probands who were not carriers (P < 0.001). Individuals are disclosing their test results to their relatives. Probands who are BRCA1- or BRCA2-positive are more likely to experience difficulty and distress with the communication of their test results to family members

OBJECTIVE: We evaluated the capability of CT to depict findings that allowed differentiation of small-bowel ischemia from intramural hemorrhage. MATERIALS AND METHODS: Findings of 35 CT examinations (19 patients with small-bowel ischemia and 16 patients with intramural hemorrhage) were analyzed by two abdominal radiologists for the degree of wall thickening, location and length of involvement (short, <or = 15 cm; medium, 16-30 cm; or long, >30 cm), presence of hemoperitoneum, and pattern of attenuation. Patency and caliber of the superior mesenteric artery and vein were noted. Diagnosis was confirmed by laboratory findings, clinical parameters, and follow-up examinations, or at surgery. A Mann-Whitney U or Fisher's exact test was used to compare the two conditions for the following features: wall thickening, location and length of involvement, presence of hemoperitoneum, and appearance of the target sign. RESULTS: Among the 35 examinations, 18 abnormal segments with intramural hemorrhage and 19 abnormal segments with ischemia were identified. (Two patients with intramural hemorrhage each had two segments involved.) Mean bowel wall thickness was 11.7 mm (range, 4-25 mm) in patients with intramural hemorrhage and 4.0 mm (range, 1-9 mm) in patients with ischemia. Length of involvement was short in 14 segments with intramural hemorrhage and medium in four segments with intramural hemorrhage; none of the segments with intramural hemorrhage had long involvement. Among the segments with ischemia, length of involvement was medium in three and long in 16; none of the ischemic segments had short involvement. Fifteen (94%) of 16 segments with intramural hemorrhage and six (32%) of 19 segments with ischemia had hemoperitoneum. Seven of the 18 segments with intramural hemorrhage and nine of the 19 with ischemia had a target sign. Segments with intramural hemorrhage exhibited a higher statistically significant degree of wall thickening (p < 0.001), a shorter length of involvement (p < 0.0001), and a higher incidence of hemoperitoneum (p < 0.001) than did segments with ischemia. The two groups were not statistically different in location of involvement (p = 0.12) or in the incidence of the target sign (p = 0.18). CONCLUSION: Although some of the CT features overlap, a short segment involvement with wall thickening of 1 cm or greater is typical of intramural hemorrhage; a long segment involvement with wall thickening of less than 1 cm is typical of ischemia

BACKGROUND AND PURPOSE: The T2-weighted MR imaging total lesion volume and Expanded Disability Status Scale (EDSS) score are two common measures of relapsing-remitting multiple sclerosis disability and pathologic abnormality. Because the whole-brain N-acetylaspartate concentration is considered to be a new marker of the disease burden, the purpose of this study was to evaluate the relationship among these three measures. METHODS: The whole-brain N-acetylaspartate concentration and T2-weighted lesion volume were quantified by using MR imaging and proton MR spectroscopy in 49 patients with relapsing-remitting multiple sclerosis (36 female and 13 male patients; average age, 39 years; age range, 24-55 years; average EDSS score, 2; range of EDSS scores, 0-6). Correlations among whole-brain N-acetylaspartate concentrations, T2-weighted lesion volumes, and EDSS scores were obtained. RESULTS: No correlation was found between whole-brain N-acetylaspartate levels and either T2-weighted lesion volumes or EDSS scores. A weak correlation was found between the EDSS scores and T2-weighted lesion volumes (P =.043, r(s) = 0.292). CONCLUSION: Despite the lack of correlation between whole-brain N-acetylaspartate concentration and the clinical disability reflected in the EDSS score, only the former evaluates the global neuronal cell disease in the entire brain, including those lesions that are occult to conventional imaging techniques

The inter- and intrasubject reproducibility of the metabolite levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), obtained with three-dimensional (3D) multivoxel proton spectroscopy (1H-MRS), was analyzed in eight healthy volunteers. Serial, back-to-back measurements on a phantom showed the methodology and instrumentation to be highly reproducible, with a median coefficient of variation (CV) of 3.8%. In the human brain, the metabolite levels' variability was larger, with intrasubject median CVs for a total of 1876 signal voxels of 13.8%, 18.5%, and 20.1% for NAA, Cr, and Cho, respectively. These variations possibly arise from small, unavoidable, +/-1-2 mm volume-of-interest (VOI) repositioning uncertainties, which vary each 0.75-cm(3) voxel's partial fluid/gray/white-matter fractions. Comparing the CVs between eight subjects in a total of 324 selected voxels gave total interindividual CVs of 15.6%, 23.3%, and 24.4%, compared with intraindividual CVs in the same voxels of 14.4%, 14.8%, and 15.3%, for NAA, Cr, and Cho, respectively. Replacing the signal(s) from each voxel by the average of itself with its six canonical neighbors reduces the intrasubject median CVs to 8.3%, 9.5%, and 9.7%. The measurement uncertainties can be reduced at a cost of either spatial resolution (by using larger voxels) or time (by performing serial follow-ups)

BACKGROUND AND PURPOSE: Although mild or moderate traumatic brain injury (TBI) is known to cause persistent neurologic sequelae, the underlying structural changes remain elusive. Our purpose was to assess decreases in the volume of brain parenchyma (VBP) in patients with TBI and to determine if clinical parameters are predictors of the extent of atrophy. METHODS: We retrospectively assessed the total VBP in 14 patients with mild or moderate TBI at more than 3 months after injury and in seven patients at two time points more than 3 months apart. VBP was calculated from whole-brain MR images and then normalized by calculating the percent VBP (%VBP) to correct for intraindividual variations in cranial size. Clinical parameters at the time of trauma were evaluated for potential predictors of atrophy. Findings were compared with those of control subjects of similar ages. RESULTS: In the single time-point analysis, brain volumes, CSF volumes, and %VBP were not significantly different between patients and control subjects. In the longitudinal analysis, the rate of decline in %VBP (0.02 versus 0.0064 U/day, P =.05) and the change in %VBP between the first and second time points (-4.16 +/- 1.68 versus -1.49 +/- 1.7, P =.022 [mean +/-SD]) were significantly greater in patients. Change in %VBP was significantly greater in patients with loss of consciousness (LOC) than in those without LOC (P =.023). CONCLUSION: Whole-brain atrophy occurs after mild or moderate TBI and is evident at an average of 11 months after trauma. Injury that produces LOC leads to more atrophy. These findings may help elucidate an etiology for the persistent or new neurologic deficits that occur months after injury

PURPOSE: To quantify the rate of concentration decline of neuronal marker N-acetylaspartate (NAA) in the entire brain of patients with relapsing-remitting multiple sclerosis (MS) in relation to healthy age-matched control subjects. MATERIALS AND METHODS: Whole-brain NAA (WBNAA) concentration was quantified in 49 patients with relapsing-remitting MS by using magnetic resonance (MR) imaging and proton MR spectroscopy. It was statistically analyzed by using Spearman rank correlation coefficients to test the intragroup relationship between WBNAA and Expanded Disability Status Scale (EDSS) score and Mann-Whitney analyses to test for differences between subgroups' EDSS scores versus previously published WBNAA values for healthy subjects, disease duration, and age. RESULTS: Analyses indicated three subgroups of WBNAA dynamics: Ten patients' conditions were 'stable,' exhibiting an insignificant change of about 0% (0.02/14.37) per year of clinically definite disease duration (P =.54); 27 patients showed 'moderate' decline, -2.8% (-0.34/12.18) per year (P <.01); and 12 patients experienced 'rapid' decline, -27.9% (-3.39/12.14) per year (P <.01). No correlation was found between WBNAA deficit, EDSS score, and age. CONCLUSION: Ascertaining an individual's NAA concentration dynamics might enable early forecast of disease course, reflect disease severity and thus influence treatment decisions, and improve clinical trial efficiency by allowing selection of candidates on the basis of WBNAA dynamics in addition to clinical status

PURPOSE: The purpose of this work was to determine the extent of disease and disease severity in the conventional MR normal-appearing gray matter (NAGM) and white matter (NAWM) in patients with relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) utilizing quantitative magnetization transfer ratio (MTR) histogram analysis. METHOD: Twenty-seven patients with MS (16 RR, 11 SP) and 16 healthy control subjects were studied. MTR was calculated in the totally segmented GM and WM without T2 lesions in each group. RESULTS: Each of the RR and SP MS patient groups had significantly smaller MTR histogram mean values in NAGM and NAWM than the healthy subjects (p </= 0.0015). SP MS patients had a significantly lower first quartile and MTR histogram peak height for NAGM only (p </= 0.004) when compared with both RR MS patients and healthy subjects. The T2 lesion load had a modest negative correlation with MTR values in both RR and SP MS, but only in NAGM. CONCLUSION: Separate analysis of GM and WM MTR histograms may allow better detection of subtle damage and better understanding of the natural history of MS disease and ultimately the response to therapeutics

The worksite is an ideal forum for cancer risk assessment. We describe here the baseline characteristics of a large cohort. Participants completed surveys that assessed a variety of risk factors and behavioral mediators. Personalized feedback letters identified cancer risks. A total of 4395 surveys were received. Cancer prevalence was 6.5% (range, 4.3% to 11.2%). The most common risk factors were lack of exercise (41%; 32% to 68%), obesity (28%; 24% to 39%), and smoking (14%; 13% to 32%). Cardiovascular risk was also common (25%; 15% to 48%). Screening was fair to good for all cancers except colon cancer. The perceived risk for cancer was less than that for cardiovascular disease (P < 0.0001). Most smokers were in the pre-contemplation phase, whereas action/maintenance phases predominated for breast and colon cancer screening. Modifiable cancer risk factors can be identified in the majority of workers. Inaccurate risk perception is an important target for future interventions

BACKGROUND AND PURPOSE: The magnetization transfer ratio (MTR) is a sensitive and quantitative identifier of underlying structural changes in the brain. We quantitatively evaluated age- and sex-related MTR changes in global gray matter (GM) and global white matter (WM) in healthy adults. METHODS: Fifty-two healthy volunteers (21 men, 31 women) aged 20-86 years underwent dual-echo fast spin-echo and magnetization transfer imaging performed with and then without a saturation pulse. GM and WM were distinguished by using a computer-assisted semiautomated segmentation technique. MTR histograms were generated for each segmented tissue in each subject and compared among age and sex groups. RESULTS: The mean, median, first quartile, and peak height of the MTR histogram were significantly lower in the older group (> or =50 years) than those in the younger group (<50 years) for both GM and WM. The age dependency of these values can be expressed in a quadratic fashion over the entire span of adulthood. The MTRs started to decline only after the age of approximately 40 years in both tissues. No statistically significant differences in MTR histogram measurements between the sexes were observed. CONCLUSION: The different MTR values for both GM and WM in the two age groups suggest that notable microscopic changes occur in GM and WM with advancing age, yet no significant sex-related variations in MTR measurements were found in these neurologically healthy adults. Such normative data based on the inherent contrast in MTRs are essential in studies of specific disorders of aging, and they may have implications for our understanding of the gross structural changes in both GM and WM in the aging brain

BACKGROUND AND PURPOSE: A technique of segmenting total gray matter (GM) and total white matter (WM) in human brain is now available. We investigated the effects of age and sex on total fractional GM (%GM) and total fractional WM (%WM) volumes by using volumetric MR imaging in healthy adults. METHODS: Fifty-four healthy volunteers (22 men, 32 women) aged 20-86 years underwent dual-echo fast spin-echo MR imaging. Total GM, total WM, and intracranial space volumes were segmented by using MR image-based computerized semiautomated software. Volumes were normalized as a percentage of intracranial volume (%GM and %WM) to adjust for variations in head size. Age and sex effects were then assessed. RESULTS: Both %GM and %WM in the intracranial space were significantly less in older subjects (> or =50 years) than in younger subjects (<50 years) (P <.0001 and P =.02, respectively). Consistently, %GM decreased linearly with age, beginning in the youngest subjects. %WM decreased in a quadratic fashion, with a greater rate beginning only in adult midlife. Although larger GM volumes were observed in men before adjustments for cranium size, no significant differences in %GM or %WM were observed between the sexes. CONCLUSION: GM volume loss appears to be a constant, linear function of age throughout adult life, whereas WM volume loss seems to be delayed until middle adult life. Both appear to be independent of sex. Quantitative analysis of %GM and %WM volumes can improve our understanding of brain atrophy due to normal aging; this knowledge may be valuable in distinguishing atrophy of disease patterns from characteristics of the normal aging process