Biomedical subjects

Thomas Benner

Publications and source records attributed to Thomas Benner.

At least 19 recordsLinked to original sources

PubMed2007

AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients.

Using MRI techniques, we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171-an oral tyrosine kinase inhibitor of VEGF receptors-has rapid onset, is prolonged but reversible, and has the significant clinical benefit of alleviating edema. Reversal of normalization began by 28 days, though some features persisted for as long as four months. Basic FGF, SDF1alpha, and viable circulating endothelial cells (CECs) increased when tumors escaped treatment, and circulating progenitor cells (CPCs) increased when tumors progressed after drug interruption. Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor.

Brain Edema↗

PubMed2006

Frontal connections and cognitive changes in normal aging rhesus monkeys: a DTI study.

Recent anatomical studies have found that cortical neurons are mainly preserved during the aging process while myelin damage and even axonal loss is prominent throughout the forebrain. We used diffusion tensor imaging (DT-MRI) to evaluate the hypothesis that during the process of normal aging, white matter changes preferentially affect the integrity of long corticocortical association fiber tracts, specifically the superior longitudinal fasciculus II and the cingulum bundle. This would disrupt communication between the frontal lobes and other forebrain regions leading to cognitive impairments. We analyzed DT-MRI datasets from seven young and seven elderly behaviorally characterized rhesus monkeys, creating fractional anisotropy (FA) maps of the brain. Significant age-related reductions in mean FA values were found for the superior longitudinal fasciculus II and the cingulum bundle, as well as the anterior corpus callosum. Comparison of these FA reductions with behavioral measures demonstrated a statistically significant linear relationship between regional FA and performance on a test of executive function. These findings support the hypothesis that alterations to the integrity of these long association pathways connecting the frontal lobe with other forebrain regions contribute to cognitive impairments in normal aging. To our knowledge this is the first investigation reporting such alterations in the aging monkey.

Aging↗

PubMed2006

White matter alterations in cerebral amyloid angiopathy measured by diffusion tensor imaging.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) represents beta-amyloid deposition in the small- and medium-sized vessels of the brain and meninges. CAA contributes to altered vessel function and is associated with white matter damage, cognitive impairment, and most salient, hemorrhagic stroke. We used diffusion tensor imaging to evaluate the anatomic distribution of white matter degeneration in participants diagnosed with advanced CAA. METHODS: Diffusion tensor imaging was obtained from 11 participants diagnosed with CAA-related intracerebral hemorrhage and 13 matched healthy control participants. Fractional anisotropy (FA) and diffusivity maps were compared using voxel based t test and region-of-interest analyses. RESULTS: FA was reduced in CAA in temporal white matter and in the splenium of the corpus callosum (P<0.001 with approximately 17% reduction in temporal white matter and 15% reduction in the splenium). FA was marginally increased in CAA in the posterior limb of the internal capsule and subthalamic gray matter regions (approximately 7% increase in subthalamic gray). FA changes were bilateral, remained significant in cluster analysis controlling for multiple comparisons, and did not depend on the hemisphere of the cerebral hemorrhage. Diffusivity was not substantially altered. CONCLUSIONS: These findings suggest that a pattern of regional brain tissue degeneration is a characteristic feature of advanced CAA.

Aged↗

PubMed2006

Mapping complex myoarchitecture in the bovine tongue with diffusion-spectrum magnetic resonance imaging.

The ability to resolve complex fiber populations in muscular tissues is important for relating tissue structure with mechanical function. To address this issue in the case of tongue, we employed diffusion spectrum imaging (DSI), an MRI method for determining three-dimensional myoarchitecture where myofiber populations are variably aligned. By specifically varying gradient field strength, molecular displacement in a tissue can be determined by Fourier-transforming the echo intensity against gradient strength at fixed gradient pulse spacing. The displacement profiles are visualized by graphing three-dimensional isocontour icons for each voxel, with the isocontour shape and size representing the magnitude and direction of the constituting fiber populations. To validate this method, we simulated a DSI experiment within the constraints of arbitrary crossing fibers, and determined that DSI accurately depicts the angular relationships between these fibers. Considering the fiber relationships in the whole bovine tongue, we compared the images obtained by DSI with those obtained by diffusion tensor imaging in an anterior slice of the lingual core, a region known to possess extensive fiber crossing. In contrast to diffusion tensor imaging, which depicts the anterior core solely as a region with low anisotropy due to the presence of mixed-orientation fiber populations, DSI shows two distinct fiber populations, with an explicit orthogonal relationship to each other. In imaging the whole lingual tissue, we discerned arrays of crossing and noncrossing fibers involving the intrinsic and extrinsic muscles, which merged at regions of interface. We conclude that DSI has the capacity to determine three-dimensional fiber orientation in structurally complex muscular tissues.

Animals↗

PubMed2006

Strategies for improving the detection of fMRI activation in trigeminal pathways with cardiac gating.

Functional magnetic resonance imaging (fMRI) has become a powerful tool for studying the normal and diseased human brain. The application of fMRI in detecting neuronal signals in the trigeminal system, however, has been hindered by low detection sensitivity due to activation artifacts caused by cardiac pulse-induced brain and brainstem movement. A variety of cardiac gating techniques have been proposed to overcome this issue, typically by phase locking the sampling to a particular time point during each cardiac cycle. We sought to compare different cardiac gating strategies for trigeminal system fMRI. In the present study, we used tactile stimuli to elicit brainstem and thalamus activation and compared the fMRI results obtained without cardiac gating and with three different cardiac gating strategies: single-echo with TR of 3 or 9 heartbeats (HBs) and dual-echo T2*-mapping EPI (TR = 2 HBs, TE = 21/55 ms). The dual-echo T2* mapping and the single-echo with TR of 2 and 3 HBs cardiac-gated fMRI techniques both increased detection rate of fMRI activation in brainstem. Activation in the brainstem and the thalamus was best detected by cardiac-gated dual-echo EPI.

Adult↗

PubMed2006

Comparison of manual and automatic section positioning of brain MR images.

The study protocol was approved by the institutional review board and was in full compliance with HIPAA guidelines. Informed consent was obtained from all patients. The purpose of this study was to prospectively compare intra- and intersubject variability of manual versus automatic magnetic resonance (MR) imaging section prescription. In two examinations, T2-weighted series were acquired with both methods. All intrasubject and three of six intersubject section prescription variances were significantly higher for manual prescription (P < .01). Root mean square errors confirmed better coregistration of the automated approach (P < .001). Automatic section prescription leads to improved reproducibility of imaging orientations for intra- and intersubject series in clinical practice.

Adult↗

PubMed2006

Three-dimensional myoarchitecture of the bovine tongue demonstrated by diffusion spectrum magnetic resonance imaging with tractography.

The anatomy of the mammalian tongue consists of an intricate array of variably aligned and extensively interwoven muscle fibers. As a result, it is particularly difficult to resolve the relationship between the tongue's microscopic anatomy and tissue-scale mechanical function. In order to address this question, we employed a method, diffusion spectrum imaging (DSI) with tractography, for displaying the macroscopic orientational properties of the tissue's constituting myofibers. DSI measures spatially variant proton displacement for a given 3D imaging segment (voxel), reflecting the principal orientation(s) of its myofibers. Tractography uses the angular similarity displayed by the principal fiber populations of multiple adjacent voxels to generate tract-like structures. DSI with tractography thus defines a unique set of tracts based on the net orientational behavior of the myofiber populations at different positions in the tissue. By this approach, we demonstrate a novel myoarchitectural pattern for the bovine tongue, consisting of short and orthogonally aligned crossing fiber tracts in the intrinsic core region, and longer, parallel-aligned fiber tracts on the tissue margins and in the regions of extrinsic fiber insertion. The identification of locally aligned myofiber populations by DSI with tractography allows us to reconsider lingual anatomy, not in conventional microscopic terms, but as a set of heterogeneously aligned and macroscopically resolved myofiber tracts. We postulate that the properties associated with these myofiber tracts predict the mechanical behavior of the tissue and thus constitute a method to relate structure and function for anatomically complex muscular tissues.

Animals↗

PubMed2006

Effect of using local arterial input functions on cerebral blood flow estimation.

PURPOSE: To investigate a previously developed method for perfusion-weighted MRI (PWI) cerebral blood flow (CBF) estimation that uses local arterial input functions (AIFs) in stroke patients, and determine its ability to correct delay and/or dispersion (D/D) errors. MATERIALS AND METHODS: Analysis was performed on dynamic susceptibility contrast data from 36 stroke patients, and CBF maps were calculated with global- and local-AIF techniques using standard SVP based methods. The ratios of these maps were calculated and the mean ratios were calculated for voxels with both normal and abnormal time to peak or width. The locations of the voxels with high locally-defined to globally-defined CBF ratios were also mapped and the average underlying concentration-time curves for these voxels were calculated. RESULTS: The ratio of CBF estimates based on local AIFs to global AIFs was on average increased for D/D voxels. The voxels in which this ratio was high were commonly concentrated in the ipsilateral hemisphere, and these voxels also displayed underlying concentration-time curves that showed delay or dispersion. Conversely, there were no such findings based on high globally-defined to locally-defined CBF ratios. CONCLUSION: The local-AIF technique results in an increase in the calculated CBF values for tissues with D/D, consistent with a reduction in the errors associated with D/D.

Adult↗

PubMed2006

Automated perfusion-weighted MRI using localized arterial input functions.

PURPOSE: To investigate the utility of an automated perfusion-weighted MRI (PWI) method for estimating cerebral blood flow (CBF) based on localized arterial input functions (AIFs) as compared to the standard method of manual global AIF selection, which is prone to deconvolution errors due to the effects of delay and dispersion of the contrast bolus. MATERIALS AND METHODS: Analysis was performed on spin- and gradient-echo EPI images from 36 stroke patients. A local AIF algorithm created an AIF for every voxel in the brain by searching out voxels with the lowest delay and dispersion, and then interpolating and spatially smoothing them for continuity. A generalized linear model (GLM) for predicting tissue outcome, and MTT lesion volumes were used to quantify the performance of the localized AIF method in comparison with global methods using ipsilateral and contralateral AIFs. RESULTS: The algorithm found local AIFs in each case without error and generated a higher area under the receiver operating characteristic (ROC) curve compared to both global-AIF methods. Similarly, the local MTT lesion volumes had the least mean squared error (MSE). CONCLUSION: Automated CBF calculation using local AIFs is feasible and appears to produce more useful CBF maps.

Adult↗

PubMed2006

Real-time RF pulse adjustment for B0 drift correction.

Although the magnetic field of an MR scanner is very stable under little or no load, it can become less stable under heavy-duty cycle conditions, such as in diffusion tensor imaging (DTI). Uncorrected, such field drifts lead to an apparent image shift along the phase-encoding direction and decreasing effectiveness of fat saturation pulses. A method is presented to adjust the center frequency of all RF pulses and the receiver in real time during the acquisition. No data postprocessing or changes to the sequence timing are necessary. In vivo acquisitions were performed to assess the prolonged effectiveness of fat saturation. Field drifts of approximately 2.5 Hz/min were measured and corrected during DTI acquisitions at b-values of up to 3000 s/mm2. The effectiveness of fat saturation diminished over the duration of an 18-min acquisition when the drift was left uncorrected. The proposed method corrects for apparent image shift and ensures continuously effective fat saturation over the duration of an acquisition.

Fats↗

PubMed2006

Real-time rigid body motion correction and shimming using cloverleaf navigators.

Subject motion during scanning can greatly reduce MRI image quality and is a major reason for discarding data in both clinical and research scanning. The quality of the high-resolution structural data used for morphometric analysis is especially compromised by subject movement because high-resolution scans are of longer duration. A method is presented that measures and corrects rigid body motion and associated first-order shim changes in real time, using a pulse sequence with embedded cloverleaf navigators and a feedback control mechanism. The procedure requires a 12-s preliminary mapping scan. A single-path, 4.2-ms cloverleaf navigator is inserted every repetition time (TR) after the readout of a 3D fast low-angle shot (FLASH) sequence, requiring no additional RF pulses and minimally impacting scan duration. Every TR, a rigid body motion estimate is made and a correction is fed back to adjust the gradients and shim offsets. Images are corrected and reconstructed on the scanner computer for immediate access. Correction for between-scan motion can be accomplished by using the same reference map for each scan repetition. Human and phantom tests demonstrated a consistent improvement in image quality if motion occurred during the acquisition.

Algorithms↗

PubMed2005

Conversion of ischemic brain tissue into infarction increases with age.

BACKGROUND AND PURPOSE: Brain regions normal on diffusion-weighted imaging (DWI) but abnormal on mean transit time (MTT) maps represent tissue at risk of infarction, yet the fate of these regions is quite variable. The imperfect correlation between tissue outcome and initial imaging parameters suggests that each patient's brain may have different susceptibility to ischemic stress. We hypothesize that age is a marker for tissue susceptibility to ischemia and thus plays a role in determining tissue outcome in human stroke. METHODS: Sixty patients with acute ischemic stroke and a region of DWI/MTT mismatch that was >20% of the DWI volume were included. All patients were scanned twice, within 12 hours of symptom onset and on day 5 or later. The percentage mismatch lost (PML) was calculated as percentage of initial DWI/MTT mismatch volume that was infarcted on the follow-up MRI. The statistical analysis explored relationships among the covariates age, Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtypes, time-to-MRI, and initial DWI, MTT volume, mean arterial blood pressure and blood glucose level at admission, and previous history of hypertension and diabetes mellitus. RESULTS: Univariate comparisons showed that age (P=0.003), hypertension (P=0.009), and diabetes mellitus (P=0.0002) were significantly associated with PML. Regression analyses showed age to be a significant covariate (P=0.02). The regression model predicted a change in PML of approximately 0.65% per year. The adjusted proportion of variance (R2) in PML that could be explained by age alone was 14%. CONCLUSIONS: Age-dependent increase in conversion of ischemic tissue into infarction suggests that age is a biological marker for the variability in tissue outcome in acute human stroke.

Adult↗

PubMed2005

On-line automatic slice positioning for brain MR imaging.

In clinical brain MR imaging protocols, the technician collects a quick localizer and manually positions the subsequent scans using the localizer as a guide. We present a method for automatic slice positioning using a rapidly acquired 3D localizer. The localizer is automatically aligned to a statistical atlas representing 40 healthy subjects. The atlas contains the probability of a given tissue type occurring at a given location in atlas space and the conditional probability distribution of the multi-spectral MRI intensity values for a given tissue class. Accurate rigid alignment of each subject to an atlas ensures that all patients' scans are acquired in a consistent manner. A further benefit is that slices are positioned consistently over time, so that scans of patients returning for follow-up imaging can be compared side-by-side to accurately monitor the progression of illness. The procedure also helps ensure that left/right asymmetries reflect true anatomy rather than being the result of oblique slice positioning relative to the underlying anatomy. The use of an atlas-based procedure eliminates the need to refer to a database of previously scanned images of the same patient and ensures corresponding alignment across scanners and sites, without requiring fiducial markers. Since the registration method is probabilistic, the registration error tends to increase smoothly in the presence of increasing noise and unusual anatomy or pathology rather than failing catastrophically. Translations and rotations relative to the atlas can be set so that planning can be done in anatomical space, rather than scanner coordinates, and stored as part of the protocol allowing standardization of slice orientations.

Algorithms↗

PubMed2005

A pilot study of normobaric oxygen therapy in acute ischemic stroke.

BACKGROUND AND PURPOSE: Therapies that transiently prevent ischemic neuronal death can potentially extend therapeutic time windows for stroke thrombolysis. We conducted a pilot study to investigate the effects of high-flow oxygen in acute ischemic stroke. METHODS: We randomized patients with acute stroke (<12 hours) and perfusion-diffusion "mismatch" on magnetic resonance imaging (MRI) to high-flow oxygen therapy via facemask for 8 hours (n=9) or room air (controls, n=7). Stroke scale scores and MRI scans were obtained at baseline, 4 hours, 24 hours, 1 week, and 3 months. Clinical deficits and MR abnormalities were compared between groups. RESULTS: Stroke scale scores were similar at baseline, tended to improve at 4 hours (during therapy) and 1 week, and significantly improved at 24 hours in hyperoxia-treated patients. There was no significant difference at 3 months. Mean (+/-SD) relative diffusion MRI lesion volumes were significantly reduced in hyperoxia-treated patients at 4 hours (87.8+/-22% versus 149.1+/-41%; P=0.004) but not subsequent time points. The percentage of MRI voxels improving from baseline "ischemic" to 4-hour "non-ischemic" values tended to be higher in hyperoxia-treated patients. Cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. These "during-therapy" benefits occurred without arterial recanalization. By 24 hours, MRI showed reperfusion and asymptomatic petechial hemorrhages in 50% of hyperoxia-treated patients versus 17% of controls (P=0.6). CONCLUSIONS: High-flow oxygen therapy is associated with a transient improvement of clinical deficits and MRI abnormalities in select patients with acute ischemic stroke. Further studies are warranted to investigate the safety and efficacy of hyperoxia as a stroke therapy.

Adult↗

PubMed2005

Transient ischemic attack with infarction: a unique syndrome?

It is debated whether transient symptoms associated with infarction (TSI) are best considered a minor ischemic stroke, a subtype of transient ischemic attack (TIA), or a separate ischemic brain syndrome. We studied clinical and imaging features to establish similarities and differences among ischemic stroke, TIA without infarction, and TSI. Eighty-seven consecutive patients with TIA and 74 patients with ischemic stroke were studied. All underwent diffusion-weighted imaging on admission. Symptom duration and infarct volume were determined in each group. Thirty-six patients (41.3%) with TIA had acute infarct(s). Although TIA-related infarcts were smaller than those associated with ischemic stroke (mean, 0.7 vs 27.3 ml; p < 0.001), there was no lesion size threshold that distinguished ischemic stroke from TSI. In contrast, the symptom duration probability density curve was not broad, but instead peaked early with only a few patients having symptoms for longer than 200 minutes. The probability density function for symptom duration was similar between TIA with or without infarction. The in-hospital recurrent ischemic stroke and TIA rate was 19.4% in patients with TSI and 1.3% in those with ischemic stroke. TIA with infarction appears to have unique features separate from TIA without infarction and ischemic stroke. We propose identifying TSI as a separate clinical syndrome with distinct prognostic features.

Aged↗

PubMed2005

Preoperative and intraoperative diffusion tensor imaging-based fiber tracking in glioma surgery.

OBJECTIVE: To investigate the intraoperative displacement of major white matter tracts during glioma resection by comparing preoperative and intraoperative diffusion tensor imaging-based fiber tracking. METHODS: In 37 patients undergoing glioma surgery, preoperative and intraoperative diffusion tensor imaging was performed with a 1.5-T magnetic resonance scanner applying an echo-planar imaging sequence with six diffusion directions. For three-dimensional tractography, we implemented a knowledge-based multiple-region-of-interest approach applying user-defined seed regions in the color-coded maps of fractional anisotropy. Tracking was initiated in both the retrograde and orthograde directions according to the direction of the principal eigenvector in each voxel of the region of interest. The tractography results were also assigned color, applying the convention used in color-coded fractional anisotropy maps. RESULTS: Preoperative and intraoperative fiber tracking was technically feasible in all patients. Fiber tract visualization gave a quick and intuitive overview of the displaced course of white matter tracts in three-dimensional space. Comparison of preoperative and intraoperative tractography depicted a marked shifting of major white matter tracts during glioma removal. Maximum white matter tract shifting ranged from -8 to +15 mm (+2.7 +/- 6.0 mm; mean +/- standard deviation); in 29.7%, an inward and in 62.2%, an outward shifting was detected. CONCLUSION: Comparing preoperative and intraoperative fiber tracking visualizes a marked shifting and deformation of major white matter tracts because of tumor removal. This shifting emphasizes the need for an intraoperative update of navigation systems during resection of deep-seated tumor portions near eloquent brain areas. Fiber tracking is a method not only for preoperative neurosurgical visualization but also for further intraoperative planning.

Adolescent↗

PubMed2004

Intraoperative diffusion-tensor MR imaging: shifting of white matter tracts during neurosurgical procedures--initial experience.

PURPOSE: To prospectively evaluate the location of white matter tracts with diffusion-tensor imaging (DTI) during neurosurgical procedures. MATERIALS AND METHODS: Ethical committee approval and signed informed consent were obtained. A 1.5-T magnetic resonance imager with an adapted rotating surgical table that is placed in a radiofrequency-shielded operating theater was used for pre- and intraoperative imaging. DTI was performed by applying an echo-planar imaging sequence with six diffusion directions in 38 patients (20 female patients, 18 male patients; age range, 7-77 years; mean age, 45.6 years) who were undergoing surgery (35 craniotomy and three burr hole procedures). Color-encoded maps of fractional anisotropy were generated by depicting white matter tracts. A rigid registration algorithm was used to compare pre- and intraoperative images. RESULTS: Intraoperative DTI was technically feasible in all patients, and no major image distortions occurred in the areas of interest. Pre- and intraoperative color-encoded maps of fractional anisotropy could be registered; these maps depicted marked and highly variable shifting of white matter tracts during neurosurgical procedures. In the 27 patients who underwent brain tumor resection, white matter tract shifting ranged from an inward shift of 8 mm to an outward shift of 15 mm (mean shift +/- standard deviation, outward shift of 2.5 mm +/- 5.8). In 16 (59%) of 27 patients, outward shifting was detected; in eight (30%), inward shifting was detected. In eight patients who underwent temporal lobe resections for drug-resistant epilepsy, shifting was only inward and ranged from 2 to 14 mm (9 mm +/- 3.3). In two of the three patients who underwent burr hole procedures, outward shifting occurred. CONCLUSION: Intraoperative DTI can depict shifting of major white matter tracts that is caused by surgical intervention.

Adolescent↗

PubMed2003

Do highly concentrated gadolinium chelates improve MR brain perfusion imaging? Intraindividually controlled randomized crossover concentration comparison study of 0.5 versus 1.0 mol/L gadobutrol.

PURPOSE: To assess the potential advantages of using a 1.0 mol/L versus 0.5 mol/L gadobutrol formulation for magnetic resonance (MR) brain perfusion imaging. MATERIALS AND METHODS: Forty-three healthy volunteers were enrolled in an intraindividually controlled, randomized crossover comparison study. Two gadobutrol formulations-0.5 and 1.0 mol/L- were randomly injected during two separate treatment periods. For intraindividual comparison of effectiveness parameters, single-section gradient-echo brain perfusion MR imaging was performed under identical conditions for both investigations. Quantitative and qualitative evaluations were performed. Differences between the two gadobutrol formulations were evaluated at analysis of covariance and tested for statistical significance (P <.05) with a t test. RESULTS: Use of 1.0 mol/L gadobutrol resulted in a significantly smaller bolus width at half maximum signal intensity decrease, a smaller mean peak time, a higher contrast and contrast-to-noise ratio between gray and white matter, and significant increases in both maximum change in transverse relaxation rate (DeltaR2max) and differences in peak enhancement in gray matter among all volunteers (P <.001). In white matter, increases in DeltaR2max (P =.262) and in differences in peak enhancement (P =.262) were smaller and not significant (P =.292). Parameter map analysis revealed improved quality and superior contrast in relative regional cerebral blood flow (P =.034) and mean transit time (P <.001). The lack of difference regarding relative regional cerebral blood volume maps was consistent with the use of the same dose of each gadobutrol formulation. CONCLUSION: Brain perfusion images obtained with 1.0 mol/L gadobutrol were superior to those obtained with 0.5 mol/L gadobutrol in healthy volunteers examined with the described MR imaging protocol.

Adult↗