Advances in imaging 2006.
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Diagnostic Imaging↗
Biomedical subjects
A Gregory Sorensen
Publications and source records attributed to A Gregory Sorensen.
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↗
The real estate factor: quantifying the impact of infarct location on stroke severity.
BACKGROUND AND PURPOSE: The severity of the neurological deficit after ischemic stroke is moderately correlated with infarct volume. In the current study, we sought to quantify the impact of location on neurological deficit severity and to delineate this impact from that of volume. METHODS: We developed atlases consisting of location-weighted values indicating the relative importance in terms of neurological deficit severity for every voxel of the brain. These atlases were applied to 80 first-ever ischemic stroke patients to produce estimates of clinical deficit severity. Each patient had an MRI and National Institutes of Health Stroke Scale (NIHSS) examination just before or soon after hospital discharge. The correlation between the location-based deficit predictions and measured neurological deficit (NIHSS) scores were compared with the correlation obtained using volume alone to predict the neurological deficit. RESULTS: Volume-based estimates of neurological deficit severity were only moderately correlated with measured NIHSS scores (r=0.62). The combination of volume and location resulted in a significantly better correlation with clinical deficit severity (r=0.79, P=0.032). CONCLUSIONS: The atlas methodology is a feasible way of integrating infarct size and location to predict stroke severity. It can estimate stroke severity better than volume alone.
Aged↗
Magnetic resonance as a cancer imaging biomarker.
Cancer is a diverse disease with many manifestations. Magnetic resonance (MR) has a wide range of sensitivities, and therefore has often been used to study cancer in humans in numerous different ways, most typically with MR spectroscopy and MR imaging. This article is not an exhaustive catalog of the use of MR in cancer, but will briefly highlight some of the many promising MR methods that have been developed, proposed, or used to focus on the problem of detecting and characterizing cancer, its treatments, and adverse effects.
Biomarkers, Tumor↗
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↗
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↗
Future prospects for fMRI in the clinic.
Functional MRI (fMRI) has tremendous clinical potential that is as yet unrealized. There are tremendous unmet medical needs that fMRI could address with significant benefit to human health. However, both medical and technical barriers prevent this benefit from accruing today. Technical barriers may be the reflexive focus of the current practitioners of fMRI, a technically savvy group. However, the real challenge lies in the medical realm, and this will require multidisciplinary and interdisciplinary work since the technical aspects of fMRI are ahead of the medical aspects. This can be seen in a range of diseases from Alzheimer's disease to schizophrenia to ischemic stroke: in each case our ability to image changes with fMRI outstrips our ability to do anything useful for the patient with them. Diagnostic imaging will always be linked in the clinic to therapeutic choices, and therefore the most powerful approach to link fMRI more directly to the clinic will be to tie fMRI to therapy development and implementation.
Brain Mapping↗
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↗
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↗
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↗
Diffusion tensor magnetic resonance imaging of brain tumors.
DTI seems to offer the possibility of adding important information to presurgical planning. Although experience is limited, DTI seems to provide useful local information about the structures near the tumor, and this seems to be useful in planning. In the future, DTI may provide an improved way to monitor intraoperative surgical procedures as well as their complications. Furthermore, evaluation of the response to treatment with chemotherapy and radiation therapy might also be possible. Although DTI has some limitations, its active investigation and further study are clearly warranted.
Journal Article↗
Intraoperative visualization of the pyramidal tract by diffusion-tensor-imaging-based fiber tracking.
Functional neuronavigation allows intraoperative visualization of cortical eloquent brain areas. Major white matter tracts, such as the pyramidal tract, can be delineated by diffusion-tensor-imaging based fiber tracking. These tractography data were integrated into 3-D datasets applied for neuronavigation by rigid registration of the diffusion images with standard anatomical image data so that their course could be superimposed onto the surgical field during resection of gliomas. Intraoperative high-field magnetic resonance imaging was used to compensate for the effects of brain shift, which amounted up to 8 mm. Despite image distortion of echo planar images, which was identified by non-linear registration techniques, navigation was reliable. In none of the 19 patients new postoperative neurological deficits were encountered. Intraoperative visualization of major white matter tracts allows save resection of gliomas near eloquent brain areas. A possible shifting of the pyramidal tract has to be taken into account after major tumor parts are resected.
Adult↗
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↗
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↗
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↗
Using imaging biomarkers to accelerate drug development and clinical trials.
There is increasing evidence that human medical imaging can help answer key questions that arise during the drug development process. Imaging modalities such as magnetic resonance imaging, computed tomography and positron emission tomography can offer significant insights into the bioactivity, pharmacokinetics and dosing of drugs, in addition to supporting registration applications. In this review, examples from oncology, neurology, psychiatry, infectious diseases and inflammatory diseases are used to illustrate the role imaging can play. We conclude with some remarks concerning new developments that will be required to significantly advance the field of pharmaco-imaging.
Animals↗
Imaging angiogenesis: applications and potential for drug development.
Recognition of the importance of angiogenesis to tumor growth and metastasis has led to efforts to develop new drugs that are targeted to angiogenic vasculature. Clinical trials of these agents are challenging, both because there is no agreed upon method of establishing the correct dosage for drugs whose mechanism of action is not primarily cytotoxic and because of the long time it takes to determine whether such drugs have a clinical effect. Therefore, there is a need for rapid and effective biomarkers to establish drug dosage and monitor clinical response. This review addresses the potential of imaging as a way to accurately and reliably assess changes in angiogenic vasculature in response to therapy. We describe the advantages and disadvantages of several imaging modalities, including positron emission tomography, x-ray computed tomography, magnetic resonance imaging, ultrasound, and optical imaging, for imaging angiogenic vasculature. We also discuss the analytic methods used to derive blood flow, blood volume, empirical semiquantitative hemodynamic parameters, and quantitative hemodynamic parameters from pharmacokinetic modeling. We examine the validity of these methods, citing studies that test correlations between data derived from imaging and data derived from other established methods, their reproducibility, and correlations between imaging-derived hemodynamic parameters and other pathologic indicators, such as microvessel density, pathology score, and disease outcome. Finally, we discuss which imaging methods are most likely to have the sensitivity and reliability required for monitoring responses to cancer therapy and describe ways in which imaging has been used in clinical trials to date.
Angiogenesis Inhibitors↗
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↗