Thanh B. Nguyen

Diagnostic Accuracy of Dynamic Contrast-Enhanced MR Imaging Using a Phase-Derived Vascular Input Function in the Preoperative Grading of Gliomas

BACKGROUND AND PURPOSE: The accuracy of tumor plasma volume and Ktrans estimates obtained with DCE MR imaging may have inaccuracies introduced by a poor estimation of the VIF. In this study, we evaluated the diagnostic accuracy of a novel technique by using a phase-derived VIF and “bookend” T1 measurements in the preoperative grading of patients with suspected gliomas. MATERIALS AND METHODS: This prospective study included 46 patients with a new pathologically confirmed diagnosis of glioma. Both magnitude and phase images were acquired during DCE MR imaging for estimates of Ktrans_ϕ and Vp_ϕ (calculated from a phase-derived VIF and bookend T1 measurements) as well as Ktrans_SI and Vp_SI (calculated from a magnitude-derived VIF without T1 measurements). RESULTS: Median Ktrans_ϕ values were 0.0041 minutes−1 (95 CI, 0.00062–0.033), 0.031 minutes−1 (0.011–0.150), and 0.088 minutes−1 (0.069–0.110) for grade II, III, and IV gliomas, respectively (P ≤ .05 for each). Median Vp_ϕ values were 0.64 mL/100 g (0.06–1.40), 0.98 mL/100 g (0.34–2.20), and 2.16 mL/100 g (1.8–3.1) with P = .15 between grade II and III gliomas and P = .015 between grade III and IV gliomas. In differentiating low-grade from high-grade gliomas, AUCs for Ktrans_ϕ, Vp_ϕ, Ktrans_SI, and Vp_SI were 0.87 (0.73–1), 0.84 (0.69–0.98), 0.81 (0.59–1), and 0.84 (0.66–0.91). The differences between the AUCs were not statistically significant. CONCLUSIONS: Ktrans_ϕ and Vp_ϕ are parameters that can help in differentiating low-grade from high-grade gliomas.

Invasive Aspergillosis of the Brain: Radiologic-Pathologic Correlation

History A 51-year-old man with a history of chronic lymphocytic leukemia presented with new cutaneous lesions. Biopsy of the eyelid revealed a diffuse large B-cell lymphoma, which was thought to represent a lymphomatous transformation of his leukemia. Four months after this diagnosis, the patient underwent an allogenic bone marrow transplantation, which was complicated by upper gastrointestinal bleeding, sepsis, graft-versus-host disease, and renal failure. Two weeks after the transplantation, a spiculated left-upper-lobe pulmonary lesion was seen on a chest radiograph. At computed tomography (CT), the lesion was shown to be cavitary. A differential diagnosis that included aspergillosis was suggested. The patient was treated empirically with antifungal treatment, including fluconazole and amphotericin B. Three weeks later, follow-up thoracic CT showed interval growth of the pulmonary nodule; bronchogenic carcinoma was then suspected. Fine-needle aspiration could not be performed because of a low platelet count. The patient remained neutropenic for approximately 6 weeks after the bone marrow transplantation, during which antifungal and antibacterial treatment was continued. He then developed left arm weakness and altered mental status. CT and magnetic resonance (MR) imaging of the brain revealed multiple ringenhancing lesions. His overall health continued to deteriorate, and follow-up MR imaging showed an increase in the size and number of cerebral lesions. The patient went into a deep coma and died a few days after his last cerebral MR imaging evaluation. Pathologic examination of the whole body including the brain was performed. Best Cases from the AFIP

Acute anterior circulation stroke: Recanalization using clot angioplasty

BACKGROUND AND PURPOSE Different strategies have been employed to recanalize acutely occluded middle cerebral and internal carotid arteries (ICA) in the setting of acute stroke including intravenous and intra-arterial tPA. However, pharmaceutical thrombolysis alone, may not be effective in patients with a large amount of clot volume (complete M1, terminal internal carotid artery). We report our initial experience with endovascular clot disruption using a soft silicone balloon in addition to intravenous or intra-arterial thrombolysis with tPA. METHODS This is a retrospective review of nine patients with symptoms of acute stroke from clot in the middle cerebral or internal carotid territories who were treated with intracranial balloon angioplasty. All patients presented with symptoms of acute anterior circulation stroke less than six hours from onset. Patients in whom computed tomography (CT) angiography confirmed the presence of large vessel clot (terminal ICA, M1 or proximal M2) were included in the study. A CT perfusion was performed providing maps of cerebral blood volume, flow and mean transit time. If the patient presented less than three hours from onset then intravenous tissue plasminogen activator (tPA) was also administered. Intra-arterial tPA was delivered into the clot. If the volume of clot was judged to be significant by the treating neurointerventionist, then a limited trial of tPA was administered intra-arterially followed by balloon angioplasty of persistant clot. The time from imaging to vessel recanalization was recorded. Clinical outcomes were assessed using the modified Rankin scale and Barthel Index. RESULTS Diagnostic CT perfusion studies were performed in 7 (78%), all of which showed a significant amount of salvageable tissue as judged by the treating neurointerventionist and neurologist. Recanalization (TIMI 2 or 3) was possible in 8 (89%). There were no cases of symptomatic intracranial hemorrhage and 2 (22%) asymptomatic hemorrhages. The average time from performance of the initial emergency CT to vessel recanalization was 2.1 hours with mean time from symptom onset to vessel recanalization of 4.1 hours. Five (56%) patients had good outcomes, 1 (11%) had mild and 3 (33%) had moderate to severe disability. CONCLUSION Clot angioplasty can potentially shorten recanalization times in well-selected patients and can be an effective complimentary procedure in patients with tPA resistant clot. Angioplasty can be performed with a very low complication rate using the technique described and may be associated with good outcomes.

Preoperative Prognostic Value of Dynamic Contrast-Enhanced MRI–Derived Contrast Transfer Coefficient and Plasma Volume in Patients with Cerebral Gliomas

BACKGROUND AND PURPOSE: The prognostic value of dynamic contrast-enhanced MR imaging–derived plasma volume obtained in tumor and the contrast transfer coefficient has not been well-established in patients with gliomas. We determined whether plasma volume and contrast transfer coefficient in tumor correlated with survival in patients with gliomas in addition to other factors such as age, type of surgery, preoperative Karnofsky score, contrast enhancement, and histopathologic grade. MATERIALS AND METHODS: This prospective study included 46 patients with a new pathologically confirmed diagnosis of glioma. The contrast transfer coefficient and plasma volume obtained in tumor maps were calculated directly from the signal-intensity curve without T1 measurements, and values were obtained from multiple small ROIs placed within tumors. Survival curve analysis was performed by dichotomizing patients into groups of high and low contrast transfer coefficient and plasma volume. Univariate analysis was performed by using dynamic contrast-enhanced parameters and clinical factors. Factors that were significant on univariate analysis were entered into multivariate analysis. RESULTS: For all patients with gliomas, survival was worse for groups of patients with high contrast transfer coefficient and plasma volume obtained in tumor (P < .05). In subgroups of high- and low-grade gliomas, survival was worse for groups of patients with high contrast transfer coefficient and plasma volume obtained in tumor (P < .05). Univariate analysis showed that factors associated with lower survival were age older than 50 years, low Karnofsky score, biopsy-only versus resection, marked contrast enhancement versus no/mild enhancement, high contrast transfer coefficient, and high plasma volume obtained in tumor (P < .05). In multivariate analysis, a low Karnofsky score, biopsy versus resection in combination with marked contrast enhancement, and a high contrast transfer coefficient were associated with lower survival rates (P < .05). CONCLUSIONS: In patients with glioma, those with a high contrast transfer coefficient have lower survival than those with low parameters.

Comparison of the Diagnostic Accuracy of DSC- and Dynamic Contrast-Enhanced MRI in the Preoperative Grading of Astrocytomas

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced MR imaging parameters can be biased by poor measurement of the vascular input function. We have compared the diagnostic accuracy of dynamic contrast-enhanced MR imaging by using a phase-derived vascular input function and “bookend” T1 measurements with DSC MR imaging for preoperative grading of astrocytomas. MATERIALS AND METHODS: This prospective study included 48 patients with a new pathologic diagnosis of an astrocytoma. Preoperative MR imaging was performed at 3T, which included 2 injections of 5-mL gadobutrol for dynamic contrast-enhanced and DSC MR imaging. During dynamic contrast-enhanced MR imaging, both magnitude and phase images were acquired to estimate plasma volume obtained from phase-derived vascular input function (Vp_Φ) and volume transfer constant obtained from phase-derived vascular input function (Ktrans_Φ) as well as plasma volume obtained from magnitude-derived vascular input function (Vp_SI) and volume transfer constant obtained from magnitude-derived vascular input function (Ktrans_SI). From DSC MR imaging, corrected relative CBV was computed. Four ROIs were placed over the solid part of the tumor, and the highest value among the ROIs was recorded. A Mann-Whitney U test was used to test for difference between grades. Diagnostic accuracy was assessed by using receiver operating characteristic analysis. RESULTS: Vp_ Φ and Ktrans_Φ values were lower for grade II compared with grade III astrocytomas (P < .05). Vp_SI and Ktrans_SI were not significantly different between grade II and grade III astrocytomas (P = .08–0.15). Relative CBV and dynamic contrast-enhanced MR imaging parameters except for Ktrans_SI were lower for grade III compared with grade IV (P ≤ .05). In differentiating low- and high-grade astrocytomas, we found no statistically significant difference in diagnostic accuracy between relative CBV and dynamic contrast-enhanced MR imaging parameters. CONCLUSIONS: In the preoperative grading of astrocytomas, the diagnostic accuracy of dynamic contrast-enhanced MR imaging parameters is similar to that of relative CBV.

Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion

BackgroundUnraveling the signaling pathways responsible for the establishment of a metastatic phenotype in carcinoma cells is critically important for understanding the pathology of cancer. The acquisition of cell motility is a key property of metastatic tumor cells and is a prerequisite for invasion. Rho GTPases regulate actin cytoskeleton reorganization and the cellular responses required for cell motility and invasion. Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates the activity of the Rho GTPases Rac1 and RhoA. DGKζ mRNA is highly expressed in several different colon cancer cell lines, as well as in colon cancer tissue relative to normal colonic epithelium, and thus may contribute to the metastatic process.MethodsTo investigate potential roles of DGKζ in cancer metastasis, a cellular, isogenic model of human colorectal cancer metastatic transition was used. DGKζ protein levels, Rac1 and RhoA activity, and PAK phosphorylation were measured in the non-metastatic SW480 adenocarcinoma cell line and its highly metastatic variant, the SW620 line. The effect of DGKζ silencing on Rho GTPase activity and invasion through Matrigel-coated Transwell inserts was studied in SW620 cells. Invasiveness was also measured in PC-3 prostate cancer and MDA-MB-231 breast cancer cells depleted of DGKζ.ResultsDGKζ protein levels were elevated approximately 3-fold in SW620 cells compared to SW480 cells. There was a concomitant increase in active Rac1 in SW620 cells, as well as substantial increases in the expression and phosphorylation of the Rac1 effector PAK1. Similarly, RhoA activity and expression were increased in SW620 cells. Knockdown of DGKζ expression in SW620 cells by shRNA-mediated silencing significantly reduced Rac1 and RhoA activity and attenuated the invasiveness of SW620 cells in vitro. DGKζ silencing in highly metastatic MDA-MB-231 breast cancer cells and PC-3 prostate cancer cells also significantly attenuated their invasiveness.ConclusionElevated DGKζ expression contributes to increased Rho GTPase activation and the enhanced motility of metastatic cancer cells. These findings warrant further investigation of the clinical relevance of DGKζ upregulation in colon and other cancers. Interfering with DGKζ function could provide a means of inhibiting invasion and metastasis.

Evaluation of Perfusion CT in Grading and Prognostication of High-Grade Gliomas at Diagnosis: A Pilot Study

OBJECTIVE Differentiation of grade 3 astrocytoma from glioblastoma multiforme can be difficult with conventional structural imaging but is important for prognosis. The purpose of this study was to assess perfusion CT in differentiating high-grade gliomas (HGGs) and their role in prognosis in the care of patients with HGG. SUBJECTS AND METHODS Twenty patients with previously untreated HGG underwent prospective evaluation with perfusion CT. Permeability surface area product (PS) and cerebral blood volume (CBV) were calculated by the deconvolution method and were compared between HGGs with Student two-sample t tests. Receiver operating characteristic curves were generated for PS, CBV, and the conjoint factor PS + CBV. Cox regression analysis was used to correlate these parameters with patient survival over a follow-up period. Hazard ratios were calculated, and Kaplan-Meier survival curves were drawn. RESULTS There was a significant difference between grade 3 and grade 4 gliomas for PS (p = 0.022) and PS + CBV (p = 0.019) but not for CBV alone (p = 0.411). Receiver operating characteristic analyses showed that PS (area under the curve [AUC], 0.72) and CBV + PS (AUC, 0.73) can be used to differentiate grade 3 from grade 4 gliomas but that CBV alone cannot be so used (AUC, 0.54). There was a significant relation between patient outcome and age (p = 0.034) and CBV + PS (p = 0.048). Patients with HGG and a CBV + PS greater than 9 had a poor outcome (hazard ratio, 6.00). CONCLUSION PS and CBV + PS can be used to differentiate grade 3 from grade 4 gliomas. The outcome of patients with HGG depends on age and CBV + PS.

Processing and interpretation times of CT angiogram and CT perfusion in stroke.

OBJECTIVE To determine the mean time for acquiring computed tomogram perfusion (CTP) and CT angiogram (CTA) images in acute stroke. To determine and compare processing and interpretation times amongst three groups of radiologists with varying degree of expertise: two radiology residents (Group I), two neuroradiology fellows (Group II) and four consultant neuroradiologists (Group III). METHODS The mean time of acquisition of CTA and CTP studies was calculated among ten patients presenting with acute stroke. All readers had to process the CTA and CTP images, interpret them (for presence or absence of thrombus and penumbra) and save them on the GE Advantage Windows workstation. The mean time for processing and interpreting these studies was calculated. RESULTS The mean time for acquisition of CTA and CTP studies in the ten patients was 14.6 +/- 5.9 minutes. The time taken for CTA processing and interpretation in Groups I, II and III was 2.3 +/- 1.3 min, 1.6 +/- 0.4 min and 1.5 +/- 0.7 min respectively. The time required for CTP processing and interpretation by the same groups was 5.2 +/- 1.7 min, 4.5 +/- 1.5 min and 4.1 +/- 1.1 min respectively. There was a statistically significant difference of means between Groups I and III in the CTA and CTP processing and interpretation times (p=0.02, p=0.01 respectively) but no statistical difference between Groups I and II (p=0.15, p=0.22 respectively) or Groups II and III (p=0.31, p=0.30 respectively). CONCLUSION The CTA and CTP studies can be performed, processed and interpreted quickly in acute stroke.

Hyperperfusion on perfusion computed tomography following revascularization for acute stroke

Purpose: To describe the findings of hyperperfusion on perfusion computed tomography (CT) in four patients following revascularization for acute stroke. Material and Methods: In 2002–2003, among a series of 6 patients presenting with an acute stroke and treated with intra-arterial thrombolysis, we observed the presence of hyperperfusion in 3 patients on the follow-up CT perfusion. We included an additional patient who was treated with intravenous thrombolysis and who had hyperperfusion on the follow-up CT perfusion. We retrospectively analyzed their CT perfusion maps. Cerebral blood volume (CBV) and cerebral blood flow (CBF) maps were compared between the affected territory and the normal contralateral hemisphere. Results: In the four patients, the mean CBV and CBF were 3.6±2.0 ml/100 g and 39±25 ml/100 g/min in the affected territory compared to the normal side (mean CBV = 2.7±2.1 ml/100 g, mean CBF = 27±23 ml/100 g/min). There was no intracranial hemorrhage in the hyperperfused territories. At follow-up CT, some hyperperfused brain areas progressed to infarction, while others retained normal white to gray matter differentiation. Conclusion: CT perfusion can demonstrate hyperperfusion, which can be seen in an ischemic brain territory following recanalization.

Radiological and Pathological Features Associated with IDH1-R132H Mutation Status and Early Mortality in Newly Diagnosed Anaplastic Astrocytic Tumours

Background Glioblastoma can occur either de novo or by the transformation of a low grade tumour; the majority of which harbor a mutation in isocitrate dehydrogenase (IDH1). Anaplastic tumours are high-grade gliomas that may represent the final step in the evolution of a secondary glioblastoma or the initial presentation of an early primary glioblastoma. We sought to determine whether pathological and/or radiological variables exist that can reliably distinguish IDH1-R132H-positive from IDH1-R132H-negative tumours and to identify variables associated with early mortality. Methods Patients diagnosed with anaplastic astrocytic tumours were included. Magnetic resonance imaging was performed and immunohistochemistry was used to identify tumours with the IDH1-R132H mutation. Survival was assessed 12 months after diagnosis. Variables associated with IDH1-R132H status were identified by univariate and ROC analysis. Results 37 gliomas were studied; 18 were positive for the IDH1-R132H mutation. No tumours demonstrated a combined loss of chromosomes 1p/19q. Patients with IDH1-R132H-positive tumours were less likely to die within 12 months of diagnosis (17% vs. 47%; p=0.046), more likely to have tumours located in the frontal lobe (55% vs. 16%; p=0.015), and have a higher minimum apparent diffusion coefficient (1.115 x 10-3 mm2/sec vs. 0.838 x 10-3 mm2/sec; p=0.016), however, these variables demonstrated only moderate strength for predicting the IDH1-R132H mutation status (AUC=0.735 and 0.711, respectively). The Ki-67 index was significantly lower in IDH1-R132H-positive tumours (0.13 vs. 0.21; p=0.034). An increased risk of death was associated with contrast-enhancement ≥ 5 cm3 in patients with IDH1-R132H-positive tumours while edema ≥ 1 cm beyond the tumour margin and < 5 mitoses/mm2 were associated with an increased risk of death in patients with IDH1-R132H-negative tumours. Conclusions IDH1-R132H-positive and -negative anaplastic tumours demonstrate unique features. Factors associated with early mortality are also dependent on IDH1-R132H status and can be used to identify patients at high risk for death.