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Biomedical subjects

James M Provenzale

Publications and source records attributed to James M Provenzale.

At least 37 records · Page 2Linked to original sources

Greater MRI lesion volumes in elderly depressed subjects than in control subjects.

Hyperintense lesions in both white matter and gray matter on T2-weighted magnetic resonance imaging (MRI) are associated with late-life depression. This large study examined differences in gray and white matter lesion volumes on brain MRI between 253 elderly depressed and 146 control subjects. White matter and gray matter lesion volumes were measured in each hemisphere using a semi-automated segmentation process and compared against depression status. Depressed subjects exhibited significantly greater total white matter (mean 7.22 ml) and gray matter (mean 0.30 ml) lesion volumes in both hemispheres than did control subjects (mean 4.87 ml in white matter and 0.18 ml in gray matter). This difference remained statistically significant even after controlling for confounders such as age, sex, race and reports of hypertension, diabetes and heart disease. Patients with late-life depression have larger white matter lesion and gray matter lesion volumes than do control subjects. Future research should combine similar volumetric techniques with methods of identifying the location of lesions specific to late-life depression.

Aged↗

Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease.

BACKGROUND: Infantile Krabbe's disease produces progressive neurologic deterioration and death in early childhood. We hypothesized that transplantation of umbilical-cord blood from unrelated donors before the development of symptoms would favorably alter the natural history of the disease among newborns in whom the disease was diagnosed because of a family history. We compared the outcomes among these newborns with the outcomes among infants who underwent transplantation after the development of symptoms and with the outcomes in an untreated cohort of affected children. METHODS: Eleven asymptomatic newborns (age range, 12 to 44 days) and 14 symptomatic infants (age range, 142 to 352 days) with infantile Krabbe's disease underwent transplantation of umbilical-cord blood from unrelated donors after myeloablative chemotherapy. Engraftment, survival, and neurodevelopmental function were evaluated longitudinally for four months to six years. RESULTS: The rates of donor-cell engraftment and survival were 100 percent and 100 percent, respectively, among the asymptomatic newborns (median follow-up, 3.0 years) and 100 percent and 43 percent, respectively, among the symptomatic infants (median follow-up, 3.4 years). Surviving patients showed durable engraftment of donor-derived hematopoietic cells with restoration of normal blood galactocerebrosidase levels. Infants who underwent transplantation before the development of symptoms showed progressive central myelination and continued gains in developmental skills, and most had age-appropriate cognitive function and receptive language skills, but a few had mild-to-moderate delays in expressive language and mild-to-severe delays in gross motor function. Children who underwent transplantation after the onset of symptoms had minimal neurologic improvement. CONCLUSIONS: Transplantation of umbilical-cord blood from unrelated donors in newborns with infantile Krabbe's disease favorably altered the natural history of the disease. Transplantation in babies after symptoms had developed did not result in substantive neurologic improvement.

Brain↗

Assessment of apparent diffusion coefficient in normal and degenerated intervertebral lumbar disks: initial experience.

PURPOSE: To determine prospectively the diffusibility of water in normal lumbar disks in adults by using the mean apparent diffusion coefficient (ADC) and to determine if a relationship exists between disk ADC and magnetic resonance (MR) findings of disk degeneration. MATERIALS AND METHODS: The study was approved by the Institutional Review Board, and all participants gave written informed consent prior to enrollment. Diffusion-weighted MR imaging of the lumbar spine was performed in 39 patients (all men; mean age, 53 years) and five volunteers (all men; mean age, 31 years). ADC values were recorded for each disk. All disks were visually graded by two independent observers as being normal or as showing at least one of three MR findings of degeneration on sagittal T2-weighted images. Mean ADC values of normal disks were compared with those of degenerated disks and were correlated with age and anatomic location. Data were analyzed by using Kendall correlation statistics, Mantel-Haenszel statistics, and a paired two-tailed Student t test. RESULTS: The mean ADC value was 2.27 x 10(-3) mm(2)/sec +/- 0.58 (+/- standard deviation) in normal disks and 2.06 x 10(-3) mm(2)/sec +/- 0.47 in abnormal disks (9% reduction, P = .006). A statistically significant dependence of lumbar disk ADC on anatomic location was reported (analysis of variance, P < .001), with lower ADC values seen in more caudal disks. There was no association between age and mean disk ADC. CONCLUSION: A statistically significant decrease was seen in the ADC values of degenerated lumbar disks when compared with ADC values of normal disks. More caudal disks, even when normal, showed lower ADC values than more cephalic disks.

Adult↗

Assessing patient utilities for varying degrees of low back pain.

RATIONALE AND OBJECTIVES: We sought to quantify patient preferences for mild, moderate, and severe low back pain via time-tradeoff analysis and utility measurement. MATERIALS AND METHODS: Forty-one patients being treated for low back pain in a tertiary care teaching hospital participated in the study. Patients were asked to decide which of three health states they were currently experiencing as well as which of the three health states was the worst experienced during their lifetime. A time-tradeoff analysis was performed, during which patients were asked the amount of time in each of the health states they would exchange for complete resolution of symptoms. We correlated (1) subjects' current health state with reported utility and (2) degree of previous low back pain with results of time-tradeoff measurements. RESULTS: All patients were willing to trade a greater number of life-years for resolution of symptoms given a more severe perceived health state. Utility decreased as severity of back pain scenarios increased, with an average utility of 0.93 +/- 0.11 for mild, 0.65 +/- 0.21 for moderate, and 0.18 +/- 0.17 for severe pain. No significant difference in time-tradeoff among subjects was identified based upon current health state on the day of interview. A statistically significant difference was seen in patients' willingness to trade time among those who had actually experienced severe pain versus those who had not. Kendall's correlation revealed that subjects who had experienced severe back pain exhibited significantly lower utilities (P < 0.01) compared with subjects who had never experienced severe pain. CONCLUSIONS: As expected, patients with severe low back pain were willing to sacrifice more potential years of life for resolution of symptoms, suggesting time-tradeoff can accurately reflect patient utility. 2. However, we found no correlation between a subject's current health state and reported utility.

Adult↗

Biological and social predictors of long-term geriatric depression outcome.

OBJECTIVE: In this study, we examined 204 older depressed individuals for up to 64 months to determine factors related to depression outcome. We hypothesized that both presence of vascular brain lesions seen on baseline magnetic resonance imaging (MRI) scans and lower baseline social support measures would be related to worse depression outcome. METHOD: At study entry, all subjects were at least 59 years old, had a diagnosis of major depression, and were free of other major psychiatric illness and primary neurological illness, including dementia and stroke. Depression was diagnosed via structured interview and clinical assessment by a geriatric psychiatrist who completed a Montgomery Asberg Depression Rating Scale (MADRS) to determine severity of depression. Subjects provided self-report data on social support variables and ability to perform basic and instrumental activities of daily living (ADL, IADL). All subjects agreed to have a baseline standardized MRI brain scan. Ratings of severity of hyperintensities were determined for the periventricular white matter, deep white matter, and subcortical gray matter by two readers who decided by consensus. Treatment was provided by geropsychiatrists following clinical guidelines. Using mixed models to analyze the data, we determined the effect of a variety of demographic, social and imaging variables on the trajectory of MADRS score, the outcome variable of interest. RESULTS: MADRS scores decreased steadily over time. In a final HLM model, in which time since entry, a baseline time indicator, age, gender, education and Mini-mental State Examination score were controlled, subjective social support, instrumental ADL impairment, subcortical gray matter severity, and the interactions of time with social network and with subcortical gray matter lesions remained significantly associated with MADRS score. CONCLUSIONS: Both social and biological factors at baseline are associated with longitudinal depression severity in geriatric depression.

Aged↗

Cortical white matter microstructural abnormalities in bipolar disorder.

This article reports on preliminary findings describing microstructural abnormalities in the white matter of cortical areas thought to be associated with bipolar disorder. In all, 14 patients with bipolar disorder and 21 nonpsychiatrically ill control subjects underwent MR imaging including a diffusion tensor imaging (DTI) pulse sequence (six directions, b=1000 mm(2)/s). DTI data were analyzed on a workstation using a program that allowed calculation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within the following three white matter fiber tracts bilaterally: the orbital frontal cortex, and the superior and middle frontal gyri. These values were compared across patient groups. The left and right orbital frontal white matter exhibited significantly higher ADC values in bipolar subjects than control subjects on both the left (p=0.028) and right (p=0.011). Microstructural changes in the white matter of the orbital frontal areas as reflected by increased ADC values appear to be associated with bipolar disorder. Further research is needed to better understand the interaction of microstructural changes and bipolar symptoms and whether these changes are specific to bipolar disorder.

Adult↗

Krabbe disease treated with hematopoietic stem cell transplantation: serial assessment of anisotropy measurements--initial experience.

PURPOSE: To prospectively compare diffusion-tensor magnetic resonance (MR) imaging anisotropy measurements of white matter (WM) regions in early and late treatment groups of Krabbe disease patients treated with stem cell transplantation. MATERIALS AND METHODS: The study was approved by the Institutional Review Board and was compliant with Health Insurance Portability and Accountability Act; informed consent was obtained from the families of all patients. Patients with early-onset Krabbe disease (four girls and three boys) underwent diffusion-tensor MR imaging before and after stem cell transplantation. Fractional anisotropy (FA) values from serial studies were compared in patients who underwent transplantation at less than 1 month (early group, two girls and one boy) and those who underwent transplantation at 5-8 months (late group, two girls and two boys). FA values were measured in the genu and splenium of the corpus callosum, the frontal WM, and the internal capsule; were compared with those of five age-matched children in the comparison group (normal MR images and no proved neurologic disease); and were expressed as a ratio. Images obtained after transplantation were evaluated at approximately 1 (n = 7), 2 (n = 6), 3 (n = 1), and 4 (n = 1) years. RESULTS: Before transplantation, mean FA ratios in the early group for all four WM regions ranged between 97% and 117%. At 1 year, mean FA ratios at all locations were either 92% or 93%. At 2 years after transplantation, mean FA ratios were between 83% and 92%. In one patient imaged at 3 years, the mean FA ratio was 97%; in another patient imaged at 4 years, the mean FA ratio was 77%. Before transplantation, mean FA ratios in the late group ranged between 55% and 74%. Mean FA ratios were between 37% and 50% at 1 year after transplantation and between 36% and 39% at 2 years. CONCLUSION: All patients had decreases in FA ratios over time. The early group had higher initial FA ratios and lower subsequent decreases, which may indicate amelioration of the dysmyelinating process.

Anisotropy↗

Determination of multiple sclerosis plaque size with diffusion-tensor MR Imaging: comparison study with healthy volunteers.

PURPOSE: To use diffusion-tensor magnetic resonance (MR) imaging to measure involvement of normal-appearing white matter (WM) immediately adjacent to multiple sclerosis (MS) plaques and thus redefine actual plaque size on diffusion-tensor images through comparison with T2-weighted images of equivalent areas in healthy volunteers. MATERIALS AND METHODS: Informed consent was not required given the retrospective nature of the study on an anonymized database. The study complied with requirements of the Health Insurance Portability and Accountability Act. Twelve patients with MS (four men, eight women; mean age, 35 years) and 14 healthy volunteers (six men, eight women; mean age, 25 years) were studied. The authors obtained fractional anisotropy (FA) values in MS plaques and in the adjacent normal-appearing WM in patients with MS and in equivalent areas in healthy volunteers. They placed regions of interest (ROIs) around the periphery of plaques and defined the total ROIs (ie, plaques plus peripheral ROIs) as abnormal if their mean FA values were at least 2 standard deviations below those of equivalent ROIs within equivalent regions in healthy volunteers. The combined area of the plaque and the peripheral ROI was compared with the area of the plaque seen on T2-weighted MR images by means of a Student paired t test (P = .05). RESULTS: The mean plaque size on T2-weighted images was 72 mm2 +/- 21 (standard deviation). The mean plaque FA value was 0.285 +/- 0.088 (0.447 +/- 0.069 in healthy volunteers [P < .001]; mean percentage reduction in FA in MS plaques, 37%). The mean plaque size on FA maps was 91 mm2 +/- 35, a mean increase of 127% compared with the size of the original plaque on T2-weighted images (P = .03). CONCLUSION: A significant increase in plaque size was seen when normal-appearing WM was interrogated with diffusion-tensor MR imaging. This imaging technique may represent a more sensitive method of assessing disease burden and may have a future role in determining disease burden and activity.

Adult↗

Quantitative analysis of diffusion tensor imaging data in serial assessment of Krabbe disease.

Krabbe disease is a rare autosomal recessive pediatric white matter (WM) disorder that is due to deficiency of a specific enzyme, beta-galactocerebrosidase. This report reviews our experience with use of diffusion tensor imaging (DTI) in serial assessment of WM changes in Krabbe disease following stem cell transplantation. DTI appears to be a sensitive means to monitor effects of stem cell transplantation on WM development in Krabbe disease. The group of early transplantation infants was clearly distinguishable from the group of late transplantation infants based on anisotropy measurements. Good correlation also was seen between neurodevelopmental scores and anisotropy measurements. The work described here in Krabbe disease may serve as a model for application of DTI to other therapies in various WM disorders such as multiple sclerosis and dysmyelinating disorders of childhood.

Anisotropy↗

A systematic guide to reviewing a manuscript.

OBJECTIVE: In this article, we provide a step-by-step guide to reviewing a manuscript that we hope will improve the quality of reviews for the AJR. CONCLUSION: We have provided a detailed series of guidelines for providing excellent reviews of manuscripts. The template we have provided can be used to serve as a checklist for important questions to ask about manuscripts during the review process. Finally, the principles presented here also can be used as a guide for authors by providing a list of important features to include during manuscript preparation and thereby prospectively address questions that good reviewers are likely to ask.

Humans↗

Association of internal carotid artery injury with carotid canal fractures in patients with head trauma.

OBJECTIVE: The purpose of our study was to determine the degree to which carotid canal fracture and other CT findings are associated with internal carotid artery (ICA) injury in patients with head trauma. MATERIALS AND METHODS: Three neuroradiologists retrospectively evaluated CT scans and cerebral angiograms of 43 patients who underwent cerebral angiography within 7 days after blunt cranial trauma over a 5-year period. Seventeen patients underwent unilateral and 26 had bilateral carotid angiography. Angiograms were evaluated for ICA injury and CT scans were evaluated for carotid canal fracture, brain contusion, subarachnoid hemorrhage, basilar skull fracture, subdural hematoma, soft-tissue swelling, sphenoid sinus air-fluid level, and other skull fracture. We recorded the number of true-positive (+CT, +angiogram), true-negative (-CT, -angiogram), false-positive (+CT, -angiogram), and false-negative (-CT, +angiogram) studies. We determined the sensitivity, specificity, positive predictive value, and negative predictive value for each CT finding. RESULTS: We identified 21 carotid canal fractures in 17 patients. Eleven ICA injuries were seen in 10 patients. Six patients with ICA injury had a carotid canal fracture. The presence of a carotid canal fracture had a sensitivity of 60% and specificity of 67% for detection of injury to the ICA passing through that canal. These values were similar to those for other CT findings. CONCLUSION: Sensitivity, specificity, positive predictive value, and negative predictive value of carotid canal fracture were only moderately good for determining the presence of ICA injury and were similar to other CT findings not typically associated with ICA injury.

Adult↗

Reviewing the reviewers: comparison of review quality and reviewer characteristics at the American Journal of Roentgenology.

OBJECTIVE: The purpose of our study was to determine which manuscript reviewer characteristics are most strongly associated with reviewer performance as judged by editors of the American Journal of Roentgenology (AJR). MATERIALS AND METHODS: At the AJR, manuscript reviews are rated by the journal editors on a subjective scale from 1 (lowest) to 4, on the basis of the value, thoroughness, and punctuality of the critique. We obtained all scores for AJR reviewers and determined the average score for each reviewer. We also sent a questionnaire to 989 reviewers requesting specific information regarding the age, sex, radiology subspecialty, number of years serving as a reviewer, academic rank, and practice type of the reviewer. The demographic profiles were correlated with the average quality score for each reviewer. Statistical analysis included correlation analysis and analysis of variance modeling. Reviewer quality scores were also correlated with the scoring of individual reviews and ultimate disposition of 196 manuscripts sent to the AJR during the same period. RESULTS: Responses to the questionnaire were obtained from 821 reviewers (83.0%), for whom quality scores were available for 714 (87.0%). Correlation analysis shows that the quality score of reviewers strongly correlated with younger age (p = 0.001). A statistically significant correlation between quality score and practice type was seen (p = 0.008), with reviewers from academic institutions receiving higher scores. No significant correlation was found between quality score and sex (p = 0.72), years of reviewing (p = 0.26), academic rank (p = 0.10), or the ultimate disposition of the manuscript (p = 0.40). The quality score of the reviewers showed no variation by subspecialty (p = 0.99). CONCLUSION: The highest-rated AJR reviewers tended to be young and from academic institutions. The quality of peer review did not correlate with the sex, academic rank, or subspecialty of the reviewer.

Female↗

The role of blood-brain barrier permeability in brain tumor imaging and therapeutics.

OBJECTIVE: Our purpose is to describe methods of assessing leakiness of the blood-brain barrier and explain mechanisms for exploiting the blood-brain barrier for therapeutic purposes. CONCLUSION: Knowledge of the workings of the blood-brain barrier is important for an understanding of the ways in which blood-brain barrier permeability may be used as a surrogate marker for drug therapeutic response. Manipulation of the blood-brain barrier may provide a means for selectively targeting tumors for drug delivery.

Animals↗

Dosimetry and radiographic analysis of 131I-labeled anti-tenascin 81C6 murine monoclonal antibody in newly diagnosed patients with malignant gliomas: a phase II study.

UNLABELLED: The objective was to perform dosimetry and evaluate dose-response relationships in newly diagnosed patients with malignant brain tumors treated with direct injections of (131)I-labeled anti-tenascin murine 81C6 monoclonal antibody (mAb) into surgically created resection cavities (SCRCs) followed by conventional external-beam radiotherapy and chemotherapy. METHODS: Absorbed doses to the 2-cm-thick shell, measured from the margins of the resection cavity interface, were estimated for 33 patients with primary brain tumors. MRI/SPECT registrations were used to assess the distribution of the radiolabeled mAb in brain parenchyma. Results from biopsies obtained from 15 patients were classified as tumor, radionecrosis, or tumor and radionecrosis, and these were correlated with absorbed dose and dose rate. Also, MRI/PET registrations were used to assess radiographic progression among patients. RESULTS: This therapeutic strategy yielded a median survival of 86 and 79 wk for all patients and glioblastoma multiforme (GBM) patients, respectively. The average SCRC residence time of (131)I-mu81C6 mAb was 76 h (range, 34-169 h). The average absorbed dose to the 2-cm cavity margins was 48 Gy (range, 25-116 Gy) for all patients and 51 Gy (range, 27-116 Gy) for GBM patients. In MRI/SPECT registrations, we observed a preferential distribution of (131)I-mu81C6 mAb through regions of vasogenic edema. An analysis of the relationship between the absorbed dose and dose rate and the first biopsy results yielded a most favorable absorbed dose of 44 Gy. A correlation between decreased survival and irreversible neurotoxicity was noted. A comparative analysis, in terms of median survival, was performed with previous brachytherapy clinical studies, which showed a proportional relationship between the average boost absorbed dose and the median survival. CONCLUSION: This study shows that (131)I-mu81C6 mAb increases the median survival of GBM patients. An optimal absorbed dose of 44 Gy to the 2-cm cavity margins is suggested to reduce the incidence of neurologic toxicity. Further clinical studies are warranted to determine the effectiveness of (131)I-mu81C6 mAb based on a target dose of 44 Gy rather than a fixed administered activity.

Adult↗

Peritumoral brain regions in gliomas and meningiomas: investigation with isotropic diffusion-weighted MR imaging and diffusion-tensor MR imaging.

PURPOSE: To retrospectively measure the diffusion-weighted (DW) imaging characteristics of peritumoral hyperintense white matter (WM) and peritumoral normal-appearing WM, as seen on T2-weighted magnetic resonance (MR) images of infiltrative high-grade gliomas and meningiomas. MATERIALS AND METHODS: Seventeen patients with biopsy-proved glioma and nine patients with imaging findings consistent with meningioma and an adjacent hyperintense region on T2-weighted MR images were examined with DW and diffusion-tensor MR imaging. Apparent diffusion coefficients (ADCs) were measured on maps generated from isotropic DW images of enhancing tumor, hyperintense regions adjacent to enhancing tumor, normal-appearing WM adjacent to hyperintense regions, and analogous locations in the contralateral WM corresponding to these areas. Fractional anisotropy (FA) was measured in similar locations on maps generated from diffusion-tensor imaging data. Changes in ADC and FA in each type of tissue were compared across tumor types by using a two-sample t test. P <.05 indicated statistical significance. RESULTS: Mean ADCs in peritumoral hyperintense regions were 1.309 x 10(-3) mm2/sec (mean percentage of 181% of normal WM) for gliomas and 1.427 x 10(-3) mm2/sec (192% of normal value) for meningiomas (no significant difference). Mean ADCs in peritumoral normal-appearing WM were 0.723 x 10(-3) mm2/sec (106% of normal value) for gliomas and 0.743 x 10(-3) mm2/sec (102% of normal value) for meningiomas (no significant difference). Mean FA values in peritumoral hyperintense regions were 0.178 (43% of normal WM value) for gliomas and 0.224 (65% of normal value) for meningiomas (P =.05). Mean FA values for peritumoral normal-appearing WM were 0.375 (83% of normal value) for gliomas and 0.404 (100% of normal value) for meningiomas (P =.01). CONCLUSION: The difference in FA decreases in peritumoral normal-appearing WM between gliomas and meningiomas was significant, and the difference in FA decreases in peritumoral hyperintense regions between these tumors approached but did not reach significance. These findings may indicate a role for diffusion MR imaging in the detection of tumoral infiltration that is not visible on conventional MR images.

Adult↗