Robert W. Prost

Utility of simultaneously acquired gradient-echo and spin-echo cerebral blood volume and morphology maps in brain tumor patients

An interleaved gradient‐echo (GE) / spin‐echo (SE) EPI sequence was used to acquire images during the first pass of a susceptibility contrast agent, in patients with brain tumors. Maps of 1) GE (total) rCBV (relative cerebral blood volume), 2) SE (microvascular) rCBV, both corrected for T1 leakage effects, and 3) (ΔR2*/ΔR2), a potential marker of averaged vessel diameter, were determined. Both GE rCBV and ΔR2*/ΔR2 correlated strongly with tumor grade (P = 0.01, P = 0.01, n = 15), while SE rCBV did not (P = 0.24, n = 15). When the GE rCBV data were not corrected for leakage effects, the correlation with tumor grade was no longer significant (P = 0.09, n = 15). These findings suggest that MRI measurements of total blood volume fraction (corrected for agent extravasation) and ΔR2*/ΔR2, as opposed to maps of microvascular volume, may prove to be the most appropriate markers for the evaluation of tumor angiogenesis (the induction of new blood vessels) and antiangiogenic therapies. Magn Reson Med 43:845–853, 2000.

Lesion-induced pseudo-dominance at functional magnetic resonance imaging: implications for preoperative assessments

OBJECTIVE:To illustrate how lesion-induced neurovascular uncoupling at functional magnetic resonance imaging (fMRI) can mimic hemispheric dominance opposite the side of a lesion preoperatively. METHODS:We retrospectively reviewed preoperative fMRI mapping data from 50 patients with focal brain abnormalities to establish patterns of hemispheric dominance of language, speech, visual, or motor system functions. Abnormalities included gliomas (31 patients), arteriovenous malformations (AVMs) (11 patients), other congenital lesions (4 patients), encephalomalacia (3 patients), and tumefactive encephalitis (1 patient). A laterality ratio of fMRI hemispheric dominance was compared with actual hemispheric dominance as verified by electrocortical stimulation, Wada testing, postoperative and posttreatment deficits, and/or lesion-induced deficits. fMRI activation maps were generated with cross-correlation (P < 0.001) or t test (P < 0.001) analysis. RESULTS:In 50 patients, a total of 85 functional areas were within 5 mm of the edge of a potentially resectable lesion. In 23 of these areas (27%), reduced fMRI signal in perilesional eloquent cortex in conjunction with preserved or increased signal in homologous contralateral brain areas revealed functional dominance opposite the side of the lesion. This suggested possible lesion-induced transhemispheric cortical reorganization to homologous brain regions (homotopic reorganization). In seven patients, however, the fMRI data were inconsistent with other methods of functional localization. In two patients with left inferior frontal gyrus gliomas and in one patient with focal tumefactive meningoencephalitis, fMRI incorrectly suggested strong right hemispheric speech dominance. In two patients with lateral precentral gyrus region gliomas and one patient with a left central sulcus AVM, the fMRI pattern incorrectly suggested primary corticobulbar motor dominance contralateral to the side of the lesion. In a patient with a right superior frontal gyrus AVM, fMRI revealed pronounced left dominant supplementary motor area activity in response to a bilateral complex motor task, but right superior frontal gyrus perilesional hemorrhage and edema subsequently caused left upper-extremity plegia. Pathophysiological factors that might have caused neurovascular uncoupling and facilitated pseudo-dominance at fMRI in these patients included direct tumor infiltration, neovascularity, cerebrovascular inflammation, and AVM-induced hemodynamic effects. Sixteen patients had proven (1 patient), probable (2 patients), or possible (13 patients) but unproven lesion-induced homotopic cortical reorganization. CONCLUSION:Lesion-induced neurovascular uncoupling causing reduced fMRI signal in perilesional eloquent cortex, in conjunction with normal or increased activity in homologous brain regions, may simulate hemispheric dominance and lesion-induced homotopic cortical reorganization.

A volumetric analysis of soft-tissue changes in the aging midface using high-resolution MRI: implications for facial rejuvenation.

Background: The present study evaluated volumetric changes in the aging midface. Both young and old living subjects were studied using high-resolution magnetic resonance imaging (MRI) to investigate the distribution and volume of the muscle and subcutaneous components of the midface. Methods: MRI with a customized radiofrequency coil was performed in 20 healthy Caucasian female volunteers equally divided between young (16 to 30 years) and old (>59 years) age groups. Sagittal oblique images were obtained at 1-mm intervals through the midface, perpendicular to the nasolabial fold. Quantitative analyses of the cheek fat pad overlying the levator labii superioris and zygomaticus major muscles were performed separately. Results: For both mimetic muscles, there were no significant differences between young and old subjects in muscle length, thickness, or volume from muscle origin to nasolabial fold. In addition, there were no significant differences between age groups in fatty infiltration of the muscles. The volumes of the medial and lateral aspects of the cheek fat pad were significantly greater in old than in young subjects (p < 0.05). In young subjects the greatest distribution of fat pad volume was found in the middle third of the cheek mass. There was a significant reduction in that portion of the fat pad distributed in the upper third and a further reduction in the lower third (p < 0.01). In old subjects, because of the increased distribution of fat in the upper third of the cheek fat pad, there was no significant difference in volume between the upper and middle thirds of the cheek fat pad. The percentage increase in fat in the upper third relative to the remainder of the midface was significantly greater in old compared with young subjects (p < 0.01). In contrast, the volume of the lower third of the midface was not significantly different between young and old subjects. Conclusions: The present study indicates that ptosis alone does not account for the changes observed in the aging midface. Selective hypertrophy of the upper portion of the cheek fat pad was also observed. The mimetic muscles, on the other hand, showed no significant differences with aging. To attain maximum precision in facial rejuvenation, these data suggest that after suspension of the ptotic cheek fat pad, each patient should be evaluated for excess bulk in the upper portion of the cheek fat pad. If excess bulk is present, patients may benefit further from selective reduction directed to the upper portion of the cheek fat pad, remaining superficial to the mimetic muscles of the face.

The Role of Diffusion Tensor Imaging in Establishing the Proximity of Tumor Borders to Functional Brain Systems: Implications for Preoperative Risk Assessments and Postoperative Outcomes:

Diffusion Tensor Imaging (DTI) is a new MRI imaging technique sensitive to directional movements of water molecules, induced by tissue barriers. This provides a new form of contrast that allows the identification of functional white matter tracts within the brain, and has been proposed as a technique suitable for presurgical planning in brain tumor patients. Resection of primary brain tumors improves survival, functional performance, and the effectiveness of adjuvant therapies, provided that surgically-induced neurological deficits can be avoided. Diffusion Tensor Imaging (DTI) has the potential to establish spatial relationships between eloquent white matter and tumor borders, provide information essential to preoperative planning, and improve the accuracy of surgical risk assessments preoperatively. We present our experience in a series of 28 brain tumor patients where the integration of functional magnetic resonance imaging (fMRI) and DTI data was used to determine key anatomic spatial relationships preoperatively. Twice as many functional systems were localized to within 5 mm of tumor borders when DTI and fMRI were utilized for preoperative planning, compared to that afforded by fMRI alone. Our results show that the combined use of fMRI and DTI can provide a better estimation of the proximity of tumor borders to eloquent brain systems sub-serving language, speech, vision, motor and premotor functions. Additionally, a low regional complication rate (4%) observed in our series suggests that preoperative planning with these combined techniques may improve surgical outcomes compared to that previously reported in the literature. Larger studies specifically designed to establish the accuracy and predictive value of DTI in brain tumor patients are warranted to substantiate our preliminary observations.

Heterogeneity in 1H-MRS profiles of presymptomatic and early manifest Huntington's disease

OBJECTIVE To evaluate (1)H-MRS profiles of the putamen in presymptomatic and manifest Huntingtons disease (HD) patients for spectroscopic markers that are reliable, consistent signs of early pathology and to look for hemispheric differences as signs of use activation in an accelerated degradative process of the dominant hemisphere. METHODS A short echo time Point RESolved Spectroscopy (PRESS) spectroscopic imaging study was performed at low field (0.5 Tesla, T) on 27 right-handed patients (17 presymptomatic gene carriers and 10 manifest patients of less than 3 years from clinical onset) and 10 right-handed normal volunteers. Spectra from individual voxels (0.56 cm(3)) in the putamen were selected for analysis. Resonance areas of peaks were normalized to water as a concentration standard. Interhemispheric comparisons were made in individuals in all three groups to look for hemispheric differences. RESULTS Two presymptomatic patients showed normal spectra but all other HD patients displayed some combination of reduced N-acetylaspartate (NAA), enhanced glutamate/glutamine (Glx) activity, and lactate (Lac) elevations or reduced creatine (Cr). Rather than showing any one metabolite as pathognomonic of early change, spectroscopic profiles showed heterogeneity between HD patients. Low creatine was common in the presymptomatic but not in the manifest group. Hemispheric ratios of abnormal metabolites showed lower values of NAA and Glx in the dominant hemisphere in all three groups but values of creatine were selectively lower in the dominant hemisphere of only the presymptomatic patients. Lac was elevated in both hemispheres but less so in the dominant hemisphere in all HD patients. CONCLUSIONS (1)H-MRS profiles from the putamen of presymptomatic and manifest patients reflect heterogeneity in pathophysiology. With the possible exception of low creatine in presymptomatic patients (1)H-MRS spectra are not suggestive of hemispheric differences supportive of an overall accelerated degradative process in the dominant hemisphere.

Cortical activation response to acoustic echo planar scanner noise.

PURPOSE Our goal was to determine the distribution of auditory and language cortex activation in response to acoustic echo planar scanner noise with functional MRI (fMRI). METHOD Acoustic scanner noise and spoken text, reproduced on high output cassette tape, were separately delivered at equivalent intensities to six normal hearing adult volunteers through earphones during fMRI data acquisition. In nine other subjects, taped scanner noise was delivered in five successive iterations of the task to assess the consistency of cortical activation to the noise stimulus. Gyri of the auditory and language system were divided into 10 different subregions for analysis of cortical activation. The number of activated pixels and proportion of volunteers activating each cortical subregion were determined using a cross-correlation analysis. RESULTS Cortical activation to taped acoustic scanner noise was present within the transverse temporal gyrus (primary auditory cortex) in all subjects, but activation was highly variable between subjects in auditory association and language relevant cortex. Auditory association cortex activation was seen in the planum polari, planum temporali, and middle temporal gyrus/superior temporal sulcus regions in one-half to two-thirds of the volunteers. There was no significant difference in the distribution of cortical activation within individual subjects across five successive iterations of the scanner noise task. Listening to spoken text consistently activated primary and association auditory cortex bilaterally as well as language relevant cortex in some cases. The mean number of activated pixels was significantly greater for text listening than acoustic scanner noise in auditory association and language relevant cortical subregions (p < 0.01), although the distribution of activity was similar between the two tasks. CONCLUSION This preliminary investigation suggests that the complex sounds produced by the echo planar pulse sequence can activate relatively large regions of auditory and language cortex bilaterally, with the extent of activation outside the primary auditory cortex being variable between subjects. However, the distribution of activation within individual subjects was relatively constant across several iterations of the scanner noise stimulus.

Spatially quantifying microscopic tumor invasion and proliferation using a voxel-wise solution to a glioma growth model and serial diffusion MRI

The purpose of this study was to develop a voxel‐wise analytical solution to a glioma growth model using serial diffusion MRI. These cell invasion, motility, and proliferation level estimates (CIMPLE maps) provide quantitative estimates of microscopic tumor growth dynamics. After an analytical solution was found, noise simulations were performed to predict the effects that perturbations in apparent diffusion coefficient values and the time between apparent diffusion coefficient map acquisitions would have on the accuracy of CIMPLE maps. CIMPLE maps were then created for 53 patients with gliomas with WHO grades of II–IV. MR spectroscopy estimates of the choline‐to‐N‐acetylaspartate ratio were compared to cell proliferation estimates in CIMPLE maps using Pearsons correlation analysis. Median differences in cell proliferation and diffusion rates between WHO grades were compared. A strong correlation (R2 = 0.9714) and good spatial correspondence were observed between MR spectroscopy measurements of the choline‐to‐N‐acetylaspartate ratio and CIMPLE map cell proliferation rate estimates. Estimates of cell proliferation and diffusion rates appear to be significantly different between low‐ (WHO II) and high‐grade (WHO III–IV) gliomas. Cell diffusion rate (motility) estimates are highly dependent on the time interval between apparent diffusion coefficient map acquisitions, whereas cell proliferation rate estimates are additionally influenced by the level of noise present in apparent diffusion coefficient maps. Magn Reson Med, 2010.

In vivo proton (H1) magnetic resonance spectroscopy for cervical carcinoma

Proton magnetic resonance spectroscopy (MRS) may be a useful tool in both the initial diagnosis of cervical carcinoma and the subsequent surveillance after radiation therapy, particularly when other standard diagnostic methods are inconclusive. Single voxel magnetic resonance (MR) spectral data were acquired from 8 normal volunteers, 16 patients with cervical cancer before radiation therapy, and 18 patients with cervical cancer after radiation therapy using an external pelvic coil at a 1.5-T on a Signa system. The presence or absence of various resonances within each spectrum was evaluated for similarities within each patient group and for spectral differences between groups. Resonances corresponding to lipid and creatine dominated the spectrum for the eight normal volunteers without detection of a choline resonance. Spectra from 16 pretreatment patients with biopsy-proven cervical cancer revealed strong resonances at a chemical shift of 3.25 ppm corresponding to choline. Data acquired from the 18 posttreatment setting studies was variable, but often correlated well with the clinical findings. Biopsy confirmation was obtained in seven patients. H1 MRS of the cervix using a noninvasive pelvic coil consistently demonstrates reproducible spectral differences between normal and neoplastic cervical tissue in vivo. However, signal is still poor for minimal disease recurrence. Further study is needed at intervals before, during, and after definitive irradiation with biopsy confirmation to validate the accuracy of MRS in distinguishing persistence or recurrence of disease from necrosis and fibrosis.

Opacification of the Genitourinary Collecting System During MDCT Urography with Enhanced CT Digital Radiography: Nonsaline Versus Saline Bolus

OBJECTIVE The purpose of this study was to determine whether a saline bolus during CT urography improves urinary collecting system opacification and whether the addition of enhanced CT digital radiography (CTDR) improves urinary collecting system visualization with or without a saline bolus. MATERIALS AND METHODS One hundred eight CT urography and enhanced CTDR examinations were reviewed. Fifty-four patients were given a saline bolus during CT urography, and 54 patients underwent CT urography without a saline bolus. Urinary collecting system opacification was evaluated by group (saline vs nonsaline), imaging technique (CT urography alone vs CT urography plus enhanced CTDR), number of enhanced CTDR images, and site of nonopacified urinary segments. Using a multivariate logistic regression model, we determined significance of variables and odds of complete opacification. RESULTS In the saline group, 248 nonopacified sites were identified on CT urography alone and 95 sites with CT urography plus enhanced CTDR. In the nonsaline group, 185 nonopacified sites were identified on CT urography alone and 59 sites with CT urography plus enhanced CTDR. Combining both groups, 433 nonopacified sites were identified with CT urography alone and 154 sites with CT urography plus enhanced CTDR. Multivariate logistic regression showed significance for group (p = 0.010), imaging method (p < 0.0001), number of enhanced CTDR images (p = 0.048), and site of segment opacification (p < 0.0001). The renal pelvis shows the greatest odds and the distal ureter the lowest odds for complete opacification by group or imaging method. CONCLUSION The addition of a saline bolus offers no improvement, whereas the addition of enhanced CTDR offers significant improvement in collecting system opacification during CT urography.

Carotid plaque regression following 6-month statin therapy assessed by 3T cardiovascular magnetic resonance: comparison with ultrasound intima media thickness

BackgroundCardiovascular magnetic resonance (CMR) allows volumetric carotid plaque measurement that has advantage over 2-dimensional ultrasound (US) intima-media thickness (IMT) in evaluating treatment response. We tested the hypothesis that 6-month statin treatment in patients with carotid plaque will lead to plaque regression when measured by 3 Tesla CMR but not by IMT.MethodsTwenty-six subjects (67 ± 2 years, 7 females) with known carotid plaque (> 1.1 mm) and coronary or cerebrovascular atherosclerotic disease underwent 3T CMR (T1, T2, proton density and time of flight sequences) and US at baseline and following 6 months of statin therapy (6 had initiation, 7 had increase and 13 had maintenance of statin dosing). CMR plaque volume (PV) was measured in the region 12 mm below and up to 12 mm above carotid flow divider using software. Mean posterior IMT in the same region was measured. Baseline and 6-month CMR PV and US IMT were compared. Change in lipid rich/necrotic core (LR/NC) and calcification plaque components from CMR were related to change in PV.ResultsLow-density lipoprotein cholesterol decreased (86 ± 6 to 74 ± 4 mg/dL, p = 0.046). CMR PV decreased 5.8 ± 2% (1036 ± 59 to 976 ± 65 mm3, p = 0.018). Mean IMT was unchanged (1.12 ± 0.06 vs. 1.14 ± 0.06 mm, p = NS). Patients with initiation or increase of statins had -8.8 ± 2.8% PV change (p = 0.001) while patients with maintenance of statin dosing had -2.7 ± 3% change in PV (p = NS). There was circumferential heterogeneity in CMR plaque thickness with greatest thickness in the posterior carotid artery, in the region opposite the flow divider. Similarly there was circumferential regional difference in change of plaque thickness with significant plaque regression in the anterior carotid region in region of the flow divider. Change in LR/NC (R = 0.62, p = 0.006) and calcification (R = 0.45, p = 0.03) correlated with PV change.ConclusionsSix month statin therapy in patients with carotid plaque led to reduced plaque volume by 3T CMR, but ultrasound posterior IMT did not show any change. The heterogeneous spatial distribution of plaque and regional differences in magnitude of plaque regression may explain the difference in findings and support volumetric measurement of plaque. 3T CMR has potential advantage over ultrasound IMT to assess treatment response in individuals and may allow reduced sample size, duration and cost of clinical trials of plaque regression.