Jaroslaw Krejza

Posttreatment recurrence of malignant brain neoplasm: Accuracy of relative cerebral blood volume fraction in discriminating low from high malignant histologic volume fraction

PURPOSE To determine the accuracy of relative cerebral blood volume (rCBV) fraction for distinguishing high-grade recurrent neoplasm from treatment-related necrosis (TRN) in enhancing masses identified on surveillance magnetic resonance (MR) images following treatment for primary or secondary brain neoplasm. MATERIALS AND METHODS This institutional review board approved and HIPAA-compliant retrospective study included 30 patients undergoing resection of recurrent enhancing mass appearing after treatment with surgery and radiation, with or without chemotherapy. The enhancing mass volume was manually segmented on three-dimensional T1-weighted images. The rCBV maps were created by using T2-weighted dynamic susceptibility contrast perfusion MR imaging and registered to T1-weighted images, and the fraction of enhancing mass with rCBV above a range of thresholds was calculated. A receiver operating characteristic (ROC) curve was created by calculating sensitivity-specificity pairs at each threshold for rCBV fraction (< or = 20% or > 20%) by using percentage of malignant features at histologic evaluation as the reference criterion. Relationships between rCBV and probability of recurrence were estimated by using logistic regression analysis. RESULTS ROC analysis showed excellent discriminating accuracy of rCBV fraction (area under the ROC curve, 0.97 +/- 0.03 [standard error]) and high efficiency (93%) with an rCBV threshold of 1.8 times that of normal-appearing white matter. Logistic regression analysis showed that a unit increase of rCBV is associated with a 254-fold increase (95% confidence interval: 43, 1504, P < .001) of the odds that enhanced tissue is recurrence, adjusting for age, treatment, volume of enhancing tissue, and time to suspected recurrence. CONCLUSION The fraction of malignant histologic features in enhancing masses recurring after treatment for brain neoplasms can be predicted by using the rCBV fraction, with improved differentiation between recurrent neoplasm and TRN.

Prediction of oligodendroglial tumor subtype and grade using perfusion weighted magnetic resonance imaging

OBJECT Treatment of patients with oligodendrogliomas relies on histopathological grade and characteristic cytogenetic deletions of 1p and 19q, shown to predict radio- and chemosensitivity and prolonged survival. Perfusion weighted magnetic resonance (MR) imaging allows for noninvasive determination of relative tumor blood volume (rTBV) and has been used to predict the grade of astrocytic neoplasms. The aim of this study was to use perfusion weighted MR imaging to predict tumor grade and cytogenetic profile in oligodendroglial neoplasms. METHODS Thirty patients with oligodendroglial neoplasms who underwent preoperative perfusion MR imaging were retrospectively identified. Tumors were classified by histopathological grade and stratified into two cytogenetic groups: 1p or 1p and 19q loss of heterozygosity (LOH) (Group 1), and 19q LOH only on intact alleles (Group 2). Tumor blood volume was calculated in relation to contralateral white matter. Multivariate logistic regression analysis was used to develop predictive models of cytogenetic profile and tumor grade. RESULTS In World Health Organization Grade II neoplasms, the rTBV was significantly greater (p < 0.05) in Group 1 (mean 2.44, range 0.96-3.28; seven patients) compared with Group 2 (mean 1.69, range 1.27-2.08; seven patients). In Grade III neoplasms, the differences between Group 1 (mean 3.38, range 1.59-6.26; four patients) and Group 2 (mean 2.83, range 1.81-3.76; 12 patients) were not significant. The rTBV was significantly greater (p < 0.05) in Grade III neoplasms (mean 2.97, range 1.59-6.26; 16 patients) compared with Grade II neoplasms (mean 2.07, range 0.96-3.28; 14 patients). The models integrating rTBV with cytogenetic profile and grade showed prediction accuracies of 68 and 73%, respectively. CONCLUSIONS Oligodendroglial classification models derived from advanced imaging will improve the accuracy of tumor grading, provide prognostic information, and have potential to influence treatment decisions.

In vivo DTI evaluation of white matter tracts in rat spinal cord.

To determine whether differences in specific spinal cord white matter (WM) tracts can be detected with in vivo DTI.

Use of magnetic perfusion-weighted imaging to determine epidermal growth factor receptor variant III expression in glioblastoma

Identification of the epidermal growth factor receptor variant III (EGFRvIII) mutation in glioblastoma has become increasingly relevant in the optimization of therapy. Traditionally, determination of tumor EGFRvIII-expression has relied on tissue-based diagnostics. Here, we assess the accuracy of magnetic resonance perfusion-weighted imaging (MR-PWI) in discriminating the EGFRvIII-expressing glioblastoma subtype. We analyzed RNA from 132 primary human glioblastoma tissue samples by reverse-transcription polymerase chain reaction (RT-PCR) for the EGFRvIII and EGFR wild-type mutations and by quantitative RT-PCR for expression of vascular endothelial growth factor (VEGF). Concurrently, 3 independent observers reviewed preoperative 1.5-Tesla (T)/SE or 3.0-Tesla (T)/GE MR perfusion images to determine the maximum relative tumor blood volume (rTBV) of each of these tumors. EGFRvIII-expressing glioblastomas showed significantly higher rTBV, compared with those tumors lacking EGFRvIII expression. This association was observed in both the 1.5T/SE (P = .000) and 3.0T/GE (P = .001) cohorts. By logistic regression analysis, combining the 2 MR system cohorts, rTBV was a very strong predictor of EGFRvIII mutation (odds ratio [rTBV] = 2.70; P = .000; McFaddens ρ(2) = 0.23). Furthermore, by receiver-operating characteristic curve analysis, rTBV discriminated EGFRvIII with very high accuracy (A(z) = 0.81). In addition, we found that VEGF upregulation was associated, although without reaching statistical significance, with EGFRvIII expression (P = .16) and with increased rTBV (F-ratio = 2.71; P = .102). These trends suggest that VEGF-mediated angiogenesis may be a potential mediator of angiogenesis to increase perfusion in EGFRvIII-expressing glioblastomas, but there are likely several other contributing factors. This study demonstrates the potential to use rTBV, a MR-PWI-derived parameter, as a noninvasive surrogate of the EGFRvIII mutation.

Differentiation between oligodendroglioma genotypes using dynamic susceptibility contrast perfusion-weighted imaging and proton MR spectroscopy.

These authors used perfusion imaging and MR spectroscopy to differentiate oligodendrogliomas with 1p/19q deletions from those with intact alleles. NAA/Cr, Cho/Cr, Glx/Cr, myo-inositol/Cr and the presence of lipids and lactate were assessed in areas of maximum perfusion in 40 patients. This study showed that as groups, integration of the MRS indices from the region containing the highest cerebral blood volume was useful in distinguishing tumors with 1p/19q abnormalities from those that did not have them. BACKGROUND AND PURPOSE: Oligodendrogliomas with 1p/19q chromosome LOH are more sensitive to chemoradiation therapy than those with intact alleles. The usefulness of dynamic susceptibility contrast–PWI-guided 1H-MRS in differentiating these 2 genotypes was tested in this study. MATERIALS AND METHODS: Forty patients with oligodendrogliomas, 1p/19q LOH (n = 23) and intact alleles (n = 17), underwent MR imaging and 2D-1H-MRS. 1H-MRS VOI was overlaid on FLAIR images to encompass the hyperintense abnormality on the largest cross-section of the neoplasm and then overlaid on CBV maps to coregister CBV maps with 1H-MRS VOI. rCBVmax values were obtained by measuring the CBV from each of the selected 1H-MRS voxels in the neoplasm and were normalized with respect to contralateral white matter. Metabolite ratios with respect to ipsilateral Cr were computed from the voxel corresponding to the rCBVmax value. Logistic regression and receiver operating characteristic analyses were performed to ascertain the best model to discriminate the 2 genotypes of oligodendrogliomas. Qualitative evaluation of conventional MR imaging characteristics (patterns of tumor border, signal intensity, contrast enhancement, and paramagnetic susceptibility effect) was also performed to distinguish the 2 groups of oligodendrogliomas. RESULTS: The incorporation of rCBVmax value and metabolite ratios (NAA/Cr, Cho/Cr, Glx/Cr, myo-inositol/Cr, and lipid + lactate/Cr) into the multivariate logistic regression model provided the best discriminatory classification with sensitivity (82.6%), specificity (64.7%), and accuracy (72%) in distinguishing 2 oligodendroglioma genotypes. Oligodendrogliomas with 1p/19q LOH were also more associated with paramagnetic susceptibility effect (P < .05). CONCLUSIONS: Our preliminary results indicate the potential of combing PWI and 1H-MRS to distinguish oligodendroglial genotypes.

Angle-corrected imaging transcranial doppler sonography versus imaging and nonimaging transcranial doppler sonography in children with sickle cell disease.

BACKGROUND AND PURPOSE: Nonimaging transcranial Doppler sonography (TCD) and imaging TCD (TCDI) are used for determination of the risk of stroke in children with sickle cell disease (SCD). The purpose was to compare angle-corrected, uncorrected TCDI, and TCD blood flow velocities in children with SCD. MATERIALS AND METHODS: A total of 37 children (mean age, 7.8 ± 3.0 years) without intracranial arterial narrowing determined with MR angiography, were studied with use of TCD and TCDI at the same session. Depth of insonation and TCDI mean velocities with and without correction for the angle of insonation in the terminal internal carotid artery (ICA) and middle (MCA), anterior (ACA), and posterior (PCA) cerebral arteries were compared with TCD velocities with use of a paired t test. RESULTS: Two arteries were not found on TCDI compared with 15 not found on TCD. Average angle of insonation in the MCA, ACA, ICA, and PCA was 31°, 44°, 25°, and 29°, respectively. TCDI and TCD mean depth of insonation for all arteries did not differ significantly; however, individual differences varied substantially. TCDI velocities were significantly lower than TCD velocities, respectively, for the right and left sides (mean ± SD): MCA, 106 ± 22 cm/s and 111 ± 33 cm/s versus 130 ± 19 cm/s and 134 ± 26 cm/s; ICA, 90 ± 14 cm/s and 98 ± 27 cm/s versus 117 ± 18 cm/s and 119 ± 23 cm/s; ACA, 74 ± 24 cm/s and 88 ± 25 cm/s versus 105 ± 23 cm/s and 105 ± 31 cm/s; and PCA, 84 ± 27 cm/s and 82 ± 21 cm/s versus 95 ± 23 cm/s and 94 ± 20 cm/s. TCD and angle-corrected TCDI velocities were not statistically different except for higher angle-corrected TCDI values in the left ACA and right PCA. CONCLUSION: TCD velocities are significantly higher than TCDI velocities but are not different from the angle-corrected TCDI velocities. TCDI identifies the major intracranial arteries more effectively than TCD.

Clinical Applications of Transcranial Color‐Coded Duplex Sonography

Transcranial color‐coded duplex sonography (TCCS), in contrast to “blind” conventional transcranial Doppler sonography (TCD), enables a sonographer to outline the intracranial bony and parenchymal structures, visualize the basal cerebral arteries in color, and measure angle‐corrected blood flow velocities in a specific site of the artery in question. This makes measurements of flow velocity more valid than those obtained with conventional TCD. TCCS is becoming a reliable tool for detecting the occlusion and narrowing of major intracranial arterial trunks. TCCS can image the collateral flow through the anterior and posterior communicating arteries in patients with unilateral, high‐grade stenosis or occlusion of the extracranial internal carotid artery, without using potentially dangerous compression tests. Large and medium‐sized arteriovenous malformations can also be detected with TCCS. The rapid sonographic assessment of cerebral hemodynamics in a neurosurgical patient with increased intracranial pressure can guide further management. The use of sonographic contrast agents can increase the number of conclusive TCCS studies in patients with insufficient acoustic windows.

Middle cerebral artery vasospasm: transcranial color-coded duplex sonography versus conventional nonimaging transcranial Doppler sonography.

Objective:To prospectively compare accuracies of transcranial color-coded duplex sonography (TCCS) and transcranial Doppler sonography (TCD) in the diagnosis of middle cerebral artery (MCA) vasospasm. Design:Prospective blinded head-to-head comparison TCD and TCCS methods using digital subtraction angiography (DSA) as the reference standard. Setting:Department of Radiology in a tertiary university health center in a metropolitan area. Patients:Eighty-one consecutive patients (mean age, 53.9 ± 13.9 years; 48 women). The indication for DSA was subarachnoid hemorrhage in 71 patients (87.6%), stroke or transient ischemic attack in five patients (6.2%), and other reasons in five patients (6.2%). Interventions:The MCA was graded as normal, narrowed <50%, and >50% using DSA. The accuracy of ultrasound methods was estimated by total area (Az) under receiver operator characteristic curve. To compare sensitivities of ultrasound methods, McNemar’s test was used with mean velocity thresholds of 120 cm/sec for the detection of less advanced, and 200 cm/sec for the more advanced MCA narrowing. Measurements and Main Results:Angiographic MCA narrowing ≤50% was found in 21, and >50% in 10 of 135 arteries. Accuracy of TCCS was insignificantly higher than that of TCD in the detection of ≤50% and >50% narrowing, total Az for mean velocity being 0.83 ± 0.05, 0.77 ± 0.05, and 0.95 ± 0.02, 0.86 ± 0.08, respectively. Sensitivity of TCCS at commonly used threshold of 120 cm/sec for less advanced MCA spasm was significantly better than that of TCD at similar specificity, 55% vs. 39%, p = 0.038, whereas at a threshold of 200 cm/sec used for more advanced spasm, sensitivities and specificities of both methods were not different. Conclusion:The accuracy of TCCS and TCD is similar, but TCCS is more sensitive than TCD in the detection of MCA spasm. Sensitivity of both techniques in the detection of mild and more advanced spasm using 120 cm/sec and 200 cm/sec thresholds, respectively, is poor; however, a larger sample is required to increase precision of our sensitivity estimates.

Suitability of Temporal Bone Acoustic Window: Conventional TCD Versus Transcranial Color‐Coded Duplex Sonography

To determine whether the proportion of patients with suitable temporal bone acoustic windows is different for conventional transcranial Doppler sonography (TCD) and transcranial color‐coded duplex sonography (TCCS), based on a head‐to‐head comparison in the same population of patients.

Twinkling artifact in color Doppler imaging of the orbit.

Objective. To show an artifact related to color Doppler flow imaging of the orbit. Methods. Three patients with strongly reflective structures in the orbit were selected from those routinely referred by clinicians for color Doppler ultrasonography of the orbit. Gray scale and color flow images were obtained with a 7.5‐MHz linear array probe for a region with strongly reflective structures. A spectral display was acquired to confirm the presence of blood flow. Results. One patient had a metallic foreign body just behind the bulb; another had calcification within the irregular mass of phthisis bulbi; and the third had hyperechoic drusen in the periphery of the intraocular melanoma. The color mosaic, suggesting the presence of blood flow, was detected beyond all hyperechoic structures. Close vertical bands with no outer wrapping were detected in the spectrum display, obtained by placing the sample volume on the region of color flow. The artificial color flow was recognized as a color Doppler twinkling artifact. Conclusions. The color flow beyond the strongly reflecting structures in the orbit might be mistakenly interpreted as real blood flow if an examiner is not familiar with the artifact. It should prompt further imaging with spectral Doppler ultrasonography.