Kyung Sik Yi

Diffusion-weighted MR imaging for the differentiation of true progression from pseudoprogression following concomitant radiotherapy with temozolomide in patients with newly diagnosed high-grade gliomas.

RATIONALE AND OBJECTIVES The assessment of the therapeutic response of high-grade gliomas treated with concomitant chemoradiotherapy (CCRT) using temozolomide is difficult because of the frequent occurrence of early imaging changes that are indistinguishable from tumor progression, termed pseudoprogression. The purpose of this study was to determine whether diffusion-weighted imaging could be used to differentiate true progression and pseudoprogression. MATERIALS AND METHODS Magnetic resonance images and diffusion-weighted images obtained within 2 months of CCRT completion in patients with high-grade gliomas were retrospectively reviewed. A total of 22 patients with increases in measurable enhancing regions were identified and classified into true progression and pseudoprogression groups on the basis of contrast-enhanced magnetic resonance images obtained 12 weeks after CCRT. Qualitative and quantitative analysis of diffusion-weighted images and apparent diffusion coefficient maps, respectively, was performed to discriminate true progression and pseudoprogression. Statistical analyses were performed using Fishers exact test, unpaired t tests, and receiver-operating characteristic analysis. RESULTS The true progression group showed a higher incidence of homogeneous or multifocal high signal intensity on diffusion-weighted images (seven of 10 patients [70%]), whereas rim high or no high signal intensity (10 of 12 [83%]) was observed in the pseudoprogression group (P = .027). True progression was defined by newly appearing or enlarged enhancing lesions with mean apparent diffusion coefficient values of 1200 × 10(-6) mm(2)/s inside the radiation field after CCRT; the sensitivity, specificity, and accuracy were 80% (eight of 10), 83.3% (10 of 12), and 81.2% (18 of 22), respectively. CONCLUSIONS The assessment of diffusion-weighted images for patients with increases of measurable enhancing regions 2 months after CCRT completion is useful for differentiating true progression from pseudoprogression.

True Progression versus Pseudoprogression in the Treatment of Glioblastomas: A Comparison Study of Normalized Cerebral Blood Volume and Apparent Diffusion Coefficient by Histogram Analysis

Objective The purpose of this study was to differentiate true progression from pseudoprogression of glioblastomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) by using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. Materials and Methods Twenty patients with histopathologically proven glioblastoma who had received CCRT with TMZ underwent perfusion-weighted imaging and diffusion-weighted imaging (b = 0, 1000 sec/mm2). The corresponding nCBV and ADC maps for the newly visible, entirely enhancing lesions were calculated after the completion of CCRT with TMZ. Two observers independently measured the histogram parameters of the nCBV and ADC maps. The histogram parameters between the true progression group (n = 10) and the pseudoprogression group (n = 10) were compared by use of an unpaired Students t test and subsequent multivariable stepwise logistic regression analysis to determine the best predictors for the differential diagnosis between the two groups. Receiver operating characteristic analysis was employed to determine the best cutoff values for the histogram parameters that proved to be significant predictors for differentiating true progression from pseudoprogression. Intraclass correlation coefficient was used to determine the level of inter-observer reliability for the histogram parameters. Results The 5th percentile value (C5) of the cumulative ADC histograms was a significant predictor for the differential diagnosis between true progression and pseudoprogression (p = 0.044 for observer 1; p = 0.011 for observer 2). Optimal cutoff values of 892 × 10-6 mm2/sec for observer 1 and 907 × 10-6 mm2/sec for observer 2 could help differentiate between the two groups with a sensitivity of 90% and 80%, respectively, a specificity of 90% and 80%, respectively, and an area under the curve of 0.880 and 0.840, respectively. There was no other significant differentiating parameter on the nCBV histograms. Inter-observer reliability was excellent or good for all histogram parameters (intraclass correlation coefficient range: 0.70-0.99). Conclusion The C5 of the cumulative ADC histogram can be a promising parameter for the differentiation of true progression from pseudoprogression of newly visible, entirely enhancing lesions after CCRT with TMZ for glioblastomas.

Correlation of apparent diffusion coefficient values measured by diffusion MRI and MGMT promoter methylation semiquantitatively analyzed with MS-MLPA in patients with glioblastoma multiforme.

To retrospectively determine whether the apparent diffusion coefficient (ADC) values correlate with O6‐methylguanine DNA methyltransferase (MGMT) promoter methylation semiquantitatively analyzed by methylation‐specific multiplex ligation‐dependent probe amplification (MS‐MLPA) in patients with glioblastoma.

Usefulness of Core Needle Biopsy for Thyroid Nodules with Macrocalcifications: Comparison with Fine-Needle Aspiration

BACKGROUND This study was performed to determine the benefits of core needle biopsy (CNB), as compared with fine-needle aspiration (FNA), for the diagnosis of thyroid nodules with macrocalcifications. MATERIALS AND METHODS The institutional review board approved this retrospective study, and informed consent was waived. From February 2010 to March 2012, the study included 147 thyroid nodules with macrocalcification of 145 consecutive patients who underwent simultaneous FNA and CNB for each nodule. Diagnostic accuracy and inconclusive diagnoses, including nondiagnostic reading and atypia of undetermined significance or follicular lesion of undetermined significance reading were compared among FNA, CNB, and a combination of FNA and CNB (FNA/CNB) using McNemars test; the benefits of CNB were calculated. RESULTS Compared to FNA, CNB and FNA/CNB showed fewer inconclusive diagnoses (FNA vs. CNB: 62/147 [42.2%] vs. 14/147 [9.5%], p<0.001; FNA vs. FNA/CNB 62/147 [42.2%] vs. 14/147 [9.5%], p<0.001), resulting in the avoidance of repeat FNA or diagnostic surgery in 48 of 62 patients (77.4%, respectively in CNB and FNA/CNB) who would have undergone these procedures if only FNA was performed. Compared to FNA, FNA/CNB showed higher sensitivity and accuracy (sensitivity: 23/32 [71.9%] vs. 31/32 [96.9%], p=0.008; accuracy: 77/86 [89.5%] vs. 85/86 [98.8%], p=0.008), resulting in avoidance of delayed surgery in eight of nine patients (88.9%) with thyroid cancer in whom the surgery would have been missed if FNA only had been performed. CONCLUSION In the workup of thyroid nodules with macrocalcification, compared with FNA alone, FNA/CNB decreases inconclusive diagnoses and increases sensitivity, thereby reducing repeated FNA procedures, diagnostic surgeries, and delayed therapeutic surgeries.

Long-term survival and differentiation of human neural stem cells in nonhuman primate brain with no immunosuppression.

Cellular fate of human neural stem cells (hNSCs) transplanted in the brain of nonhuman primates (NHPs) with no immunosuppression was determined at 22 and 24 months posttransplantation (PTx) regarding survival, differentiation, and tumorigenesis. Survival of hNSCs labeled with magnetic nanoparticles was successfully detected around injection sites in the brain at 22 months PTx by MRI. Histological examination of brain sections with H&E and Prussian blue staining at 24 months revealed that most of the grafted hNSCs were found located along the injection tract. Grafted hNSCs were found to differentiate into neurons at 24 months PTx. In addition, none of the grafted hNSCs were bromodeoxyuridine positive in the monkey brain, indicating that hNSCs did not replicate in the NHP brain and did not cause tumor formation. This study serves as a proof of principle and provides evidence that hNSCs transplanted in NHP brain could survive and differentiate into neurons in the absence of immunosuppression. It also serves as a preliminary study in our scheduled preclinical studies of hNSC transplantation in NHP stroke models.

Efficacy of diffusion-weighted magnetic resonance imaging performed before therapeutic hypothermia in predicting clinical outcome in comatose cardiopulmonary arrest survivors

AIM OF THE STUDY To develop a clinically relevant and qualitative brain magnetic resonance imaging (MRI) scoring system for acute stage comatose cardiac arrest patients. METHODS Consecutive comatose post-cardiopulmonary arrest patients were prospectively enrolled. Routine brain MRI sequences were scored by two independent and blinded experts. Predefined brain regions were qualitatively scored on diffusion-weighted imaging (DWI) sequences according to the severity of the abnormality on a scale from 0 to 4. The mean score provided by the raters determined poor outcome defined under the Cerebral Performance Categories 3, 4, or 5. DWI scans were repeated after therapeutic hypothermia (TH). The same qualitative scoring system was applied and results were compared to the initial scores. RESULTS Out of 24 recruited patients, 19 with brain MRI scans were included. Of the 19 included patients, seven showed a good outcome at hospital discharge and 12 patients showed poor neurologic outcome. Median time from the arrest to the initial DWI was 166min (IQR 114-240min). At 100% specificity, the overall, cortex, and cortex plus deep grey nuclei scores predicted poor patient outcome with a sensitivity of 91.7-100% (95% CI). Follow-up DWI scans after TH showed worse results than initial scans. CONCLUSION A qualitative MRI scoring system effectively assessed the severity of hypoxic-ischaemic brain injury following cardiopulmonary arrest. The scoring system may provide useful prognostic information in comatose cardiopulmonary arrest patients.

Comparison of brain computed tomography and diffusion-weighted magnetic resonance imaging to predict early neurologic outcome before target temperature management comatose cardiac arrest survivors

AIM We previously reported that diffusion-weighted magnetic resonance imaging (DW-MRI) could be used to predict neurologic outcomes before targeted temperature management (TTM) after return of spontaneous circulation (ROSC) from cardiac arrest (CA). We compared the efficacy of brain computed tomography (CT) and DW-MRI to predict neurologic outcome before TTM in comatose cardiac arrest survivors. METHODS We performed a retrospective study of CA patients treated with TTM. The brain CT and DW-MRI were both obtained before TTM. We analysed the grey matter to white matter ratio (GWR) on the brain CT and the presence of high signal intensity on DW-MRI, alone or in combination, to predict poor neurologic outcome (CPC 3-5). RESULTS Of 47 comatose CA patients treated with TTM, 39 patients with brain CT and DW-MRI data were included. Median time from the ROSC to the brain CT and DW-MRI was 90min (52-150) and 175min (118-240), respectively. There was no significant difference in predicting poor neurologic outcome between average GWR (area under the curve [AUC] 0.891, sensitivity/specificity 78.8%/100%) and DW-MRI (AUC 0.894, sensitivity/specificity 75.8%/100%) (p=0.963). The combination of average GWR and DW-MRI (AUC 0.939, sensitivity/specificity 87.9%/100%) improved the prediction of poor neurologic outcome rather than each one alone and in other combinations. CONCLUSION Our preliminary finding suggests that DW-MRI is potentially useful for early prediction of neurologic outcome (i.e., before TTM) in CA patients. The combination of GWR on brain CT and that on DW-MRI, rather than on each modality alone, appears to improve the sensitivity for predicting neurologic outcome after ROSC from CA. Large prospective multicenter studies should be conducted to confirm these results.

Sustained diffusion reversal with in-bore reperfusion in monkey stroke models: Confirmed by prospective magnetic resonance imaging

Although early diffusion lesion reversal after recanalization treatment of acute ischaemic stroke has been observed in clinical settings, the reversibility of lesions observed by diffusion-weighted imaging remains controversial. Here, we present consistent observations of sustained diffusion lesion reversal after transient middle cerebral artery occlusion in a monkey stroke model. Seven rhesus macaques were subjected to endovascular transient middle cerebral artery occlusion with in-bore reperfusion confirmed by repeated prospective diffusion-weighted imaging. Early diffusion lesion reversal was defined as lesion reversal at 3 h after reperfusion. Sustained diffusion lesion reversal was defined as the difference between the ADC-derived pre-reperfusion maximal ischemic lesion volume (ADCD-P Match) and the lesion on 4-week follow-up FLAIR magnetic resonance imaging. Diffusion lesions were spatiotemporally assessed using a 3-D voxel-based quantitative technique. The ADCD-P Match was 9.7 ± 6.0% (mean ± SD) and the final infarct was 1.2–6.0% of the volume of the ipsilateral hemisphere. Early diffusion lesion reversal and sustained diffusion lesion reversal were observed in all seven animals, and the calculated percentages compared with their ADCD-P Match ranged from 8.3 to 51.9% (mean ± SD, 26.9 ± 15.3%) and 41.7–77.8% (mean ± SD, 65.4 ± 12.2%), respectively. Substantial sustained diffusion lesion reversal and early reversal were observed in all animals in this monkey model of transient focal cerebral ischaemia.

Multimodal Imaging Follow-up of a Thrombosed Developmental Venous Anomaly: CT, CT Angiography and Digital Subtraction Angiography

We report a rare case of thrombosed developmental venous anomaly (DVA) in a 31-year old male with hemorrhagic cerebral venous infarction at the initial clinical presentation. In this case, sequential CT, CT angiography and digital subtraction angiography demonstrated thrombotic obstruction of the venous drainage from DVA, its progressive recanalization and temporal evolution of the affected brain parenchyma. The relevant previous literatures were reviewed and summarized.

Identification of hyperacute ischemic stroke with a more homogenous nature

Previous reports revealed that middle cerebral artery occlusion (MCAO) models in rats were very diverse in nature, and experimental stroke of a more homogenous nature had not been previously documented. This paper aims to present our novel observations of experimental stroke in rats with similar MRI characteristics after MCAO. Immediately after MCAO, 19 rats were placed into a 4.7 T MRI scanner, and diffusion weighted imaging (DWI) of axial and coronal planes was repeated every 10 minutes up to post-occlusion 115 minutes. Apparent diffusion coefficient (ADC) values of the ischemic lesions were calculated and compared to those of the unaffected contra-lateral hemispheres. Successful MCAO was defined when the whole left MCA territory showed ADC abnormality on DWI. Percentage of hemispheric lesion volume (% HLV), relative ADC value (rADC), and relative DWI signal intensity (rDWI) were serially evaluated for quantitative analysis of ADC-derived lesion characteristics. Successful MCA territorial infarction was induced in nine rats (9/19, 47.4%). In quantitative analysis of ADC-derived lesion characteristics, lesion volumes of seven rats (group 1) were very similar, but larger than those of the other two rats (group 2): % HLV of initial MRI = 45.4 ± 2.5 / 19.1 ± 6.6. rADCs and rDWIs of group 1 showed similar patterns of temporal change, which was different from those of group 2. Using prospective diffusion MRI after MCAO in rats, we identified territorial hyperacute ischemic lesions with similar MRI characteristics. This observation would contribute to the establishment of more homogenous rodent models for ischemic stroke translational research.