Validation of Ultrasound and Computed Tomography-Based Risk Stratification System and Biopsy Criteria for Cervical Lymph Nodes in Preoperative Patients With Thyroid Cancer

Objective@#This study aimed to validate the risk stratification system (RSS) and biopsy criteria for cervical lymph nodes (LNs) proposed by the Korean Society of Thyroid Radiology (KSThR). @*Materials and Methods@#This retrospective study included a consecutive series of preoperative patients with thyroid cancer who underwent LN biopsy, ultrasound (US), and computed tomography (CT) between December 2006 and June 2015. LNs were categorized as probably benign, indeterminate, or suspicious according to the current US- and CT-based RSS and the size thresholds for cervical LN biopsy as suggested by the KSThR. The diagnostic performance and unnecessary biopsy rates were calculated. @*Results@#A total of 277 LNs (53.1% metastatic) in 228 patients (mean age ± standard deviation, 47.4 years ± 14) were analyzed. In US, the malignancy risks were significantly different among the three categories (all P 5 mm LNs, P ≥ 0.177). The criteria covering only suspicious LNs showed higher specificity and lower unnecessary biopsy rates than the current criteria, while maintaining sensitivity in all imaging modalities. @*Conclusion@#Integrative evaluation of US and CT helps in reducing the proportion of indeterminate LNs and the malignancy risk among them. Nodal size did not affect the malignancy risk of LNs, and the addition of indeterminate LNs to biopsy candidates did not have an advantage in detecting LN metastases in all imaging modalities.

Myelin Content in Mild Traumatic Brain Injury Patients with Post-Concussion Syndrome: Quantitative Assessment with a Multidynamic Multiecho Sequence

Objective@#This study aimed to explore the myelin volume change in patients with mild traumatic brain injury (mTBI) with post-concussion syndrome (PCS) using a multidynamic multiecho (MDME) sequence and automatic whole-brain segmentation. @*Materials and Methods@#Forty-one consecutive mTBI patients with PCS and 29 controls, who had undergone MRI including the MDME sequence between October 2016 and April 2018, were included. Myelin volume fraction (MVF) maps were derived from the MDME sequence. After three dimensional T1-based brain segmentation, the average MVF was analyzed at the bilateral cerebral white matter (WM), bilateral cerebral gray matter (GM), corpus callosum, and brainstem. The Mann–Whitney U-test was performed to compare MVF and myelin volume between patients with mTBI and controls. Myelin volume was correlated with neuropsychological test scores using the Spearman rank correlation test. @*Results@#The average MVF at the bilateral cerebral WM was lower in mTBI patients with PCS (median [interquartile range], 25.2% [22.6%–26.4%]) than that in controls (26.8% [25.6%–27.8%]) (p = 0.004). The region-of-interest myelin volume was lower in mTBI patients with PCS than that in controls at the corpus callosum (1.87 cm3 [1.70–2.05 cm3 ] vs. 2.21 cm3 [1.86– 3.46 cm3 ]; p = 0.003) and brainstem (9.98 cm3 [9.45–11.00 cm3 ] vs. 11.05 cm3 [10.10–11.53 cm3 ]; p = 0.015). The total myelin volume was lower in mTBI patients with PCS than that in controls at the corpus callosum (0.45 cm3 [0.39–0.48 cm3 ] vs. 0.48 cm3 [0.45–0.54 cm3 ]; p = 0.004) and brainstem (1.45 cm3 [1.28–1.59 cm3 ] vs. 1.54 cm3 [1.42–1.67 cm3 ]; p = 0.042). No significant correlation was observed between myelin volume parameters and neuropsychological test scores, except for the total myelin volume at the bilateral cerebral WM and verbal learning test (delayed recall) (r = 0.425; p = 0.048). @*Conclusion@#MVF quantified from the MDME sequence was decreased at the bilateral cerebral WM in mTBI patients with PCS. The total myelin volumes at the corpus callosum and brainstem were decreased in mTBI patients with PCS due to atrophic changes.

Blood-Brain Barrier Disruption in Mild Traumatic Brain Injury Patients with Post-Concussion Syndrome: Evaluation with Region-Based Quantification of Dynamic Contrast-Enhanced MR Imaging Parameters Using Automatic Whole-Brain Segmentation

Objective@#This study aimed to investigate the blood-brain barrier (BBB) disruption in mild traumatic brain injury (mTBI) patients with post-concussion syndrome (PCS) using dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging and automatic whole brain segmentation. @*Materials and Methods@#Forty-two consecutive mTBI patients with PCS who had undergone post-traumatic MR imaging, including DCE MR imaging, between October 2016 and April 2018, and 29 controls with DCE MR imaging were included in this retrospective study. After performing three-dimensional T1-based brain segmentation with FreeSurfer software (Laboratory for Computational Neuroimaging), the mean Ktrans and vp from DCE MR imaging (derived using the Patlak model and extended Tofts and Kermode model) were analyzed in the bilateral cerebral/cerebellar cortex, bilateral cerebral/cerebellar white matter (WM), and brainstem. Ktrans values of the mTBI patients and controls were calculated using both models to identify the model that better reflected the increased permeability owing to mTBI (tendency toward higher Ktrans values in mTBI patients than in controls). The Mann-Whitney U test and Spearman rank correlation test were performed to compare the mean Ktrans and vp between the two groups and correlate Ktrans and vp with neuropsychological tests for mTBI patients. @*Results@#Increased permeability owing to mTBI was observed in the Patlak model but not in the extended Tofts and Kermode model. In the Patlak model, the mean Ktrans in the bilateral cerebral cortex was significantly higher in mTBI patients than in controls (p = 0.042). The mean vp values in the bilateral cerebellar WM and brainstem were significantly lower in mTBI patients than in controls (p = 0.009 and p = 0.011, respectively). The mean Ktrans of the bilateral cerebral cortex was significantly higher in patients with atypical performance in the auditory continuous performance test (commission errors) than in average or good performers (p = 0.041). @*Conclusion@#BBB disruption, as reflected by the increased Ktrans and decreased vp values from the Patlak model, was observed throughout the bilateral cerebral cortex, bilateral cerebellar WM, and brainstem in mTBI patients with PCS.

Prediction of Prognosis in Glioblastoma Using Radiomics Features of Dynamic Contrast-Enhanced MRI

Objective@#To develop a radiomics risk score based on dynamic contrast-enhanced (DCE) MRI for prognosis prediction in patients with glioblastoma. @*Materials and Methods@#One hundred and fifty patients (92 male [61.3%]; mean age ± standard deviation, 60.5 ± 13.5 years) with glioblastoma who underwent preoperative MRI were enrolled in the study. Six hundred and forty-two radiomic features were extracted from volume transfer constant (Ktrans), fractional volume of vascular plasma space (Vp), and fractional volume of extravascular extracellular space (Ve) maps of DCE MRI, wherein the regions of interest were based on both T1-weighted contrast-enhancing areas and non-enhancing T2 hyperintense areas. Using feature selection algorithms, salient radiomic features were selected from the 642 features. Next, a radiomics risk score was developed using a weighted combination of the selected features in the discovery set (n = 105); the risk score was validated in the validation set (n = 45) by investigating the difference in prognosis between the “radiomics risk score” groups. Finally, multivariable Cox regression analysis for progression-free survival was performed using the radiomics risk score and clinical variables as covariates. @*Results@#16 radiomic features obtained from non-enhancing T2 hyperintense areas were selected among the 642 features identified. The radiomics risk score was used to stratify high- and low-risk groups in both the discovery and validation sets (both p < 0.001 by the log-rank test). The radiomics risk score and presence of isocitrate dehydrogenase (IDH) mutation showed independent associations with progression-free survival in opposite directions (hazard ratio, 3.56; p = 0.004 and hazard ratio, 0.34; p = 0.022, respectively). @*Conclusion@#We developed and validated the “radiomics risk score” from the features of DCE MRI based on non-enhancing T2 hyperintense areas for risk stratification of patients with glioblastoma. It was associated with progression-free survival independently of IDH mutation status.

Cerebrovascular Reservoir and Arterial Transit Time Changes Assessed by Acetazolamide-Challenged Multi-Phase Arterial Spin Labeling Perfusion MRI in Chronic Cerebrovascular Steno-Occlusive Disease

Purpose@#To explore cerebrovascular reservoir (CVR) and arterial transit time (ATT) changes using acetazolamide-challenged multi-phase arterial spin labeling (MP-ASL) perfusion-weighted MRI in chronic cerebrovascular steno-occlusive disease. @*Materials and Methods@#This retrospective study enrolled patients with chronic steno-occlusion who underwent acetazolamide-challenged MP-ASL between June 2019 and October 2020.Cerebral blood flow, CVR, basal ATT, and ATT changes associated with severe stenosis, total occlusion, and chronic infarction lesions were compared. @*Results@#There were 32 patients (5 with bilateral steno-occlusion) in our study sample. The CVR was significantly reduced during total occlusion compared with severe stenosis (26.2% ± 28.8% vs. 41.4% ± 34.1%, respectively, p = 0.004). The ATT changes were not significantly different (p = 0.717). The CVR was marginally lower in patients with chronic infarction (29.6% ± 39.1% vs. 38.9% ± 28.7%, respectively, p = 0.076). However, the ATT was less shortened in pa-tients with chronic infarction (-54 ± 135 vs. -117 ± 128 ms, respectively, p = 0.013). @*Conclusion@#Acetazolamide-challenged MP-ASL provides an MRI-based CVR evaluation tool for chronic steno-occlusive disease.

Assessment of Mild Cognitive Impairment in Elderly Subjects Using a Fully Automated Brain Segmentation Software

Purpose@#Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD). Brain atrophy in this disease spectrum begins in the medial temporal lobe structure, which can be recognized by magnetic resonance imaging. To overcome the unsatisfactory inter-observer reliability of visual evaluation, quantitative brain volumetry has been developed and widely investigated for the diagnosis of MCI and AD. The aim of this study was to assess the prediction accuracy of quantitative brain volumetry using a fully automated segmentation software package, NeuroQuant®, for the diagnosis of MCI. @*Materials and Methods@#A total of 418 subjects from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease cohort were included in our study. Each participant was allocated to either a cognitively normal old group (n = 285) or an MCI group (n = 133). Brain volumetric data were obtained from T1-weighted images using the NeuroQuant software package. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to investigate relevant brain regions and their prediction accuracies. @*Results@#Multivariate logistic regression analysis revealed that normative percentiles of the hippocampus (P < 0.001), amygdala (P = 0.003), frontal lobe (P = 0.049), medial parietal lobe (P = 0.023), and third ventricle (P = 0.012) were independent predictive factors for MCI. In ROC analysis, normative percentiles of the hippocampus and amygdala showed fair accuracies in the diagnosis of MCI (area under the curve: 0.739 and 0.727, respectively). @*Conclusion@#Normative percentiles of the hippocampus and amygdala provided by the fully automated segmentation software could be used for screening MCI with a reasonable post-processing time. This information might help us interpret structural MRI in patients with cognitive impairment.

Prediction of Prognosis in Glioblastoma Using Radiomics Features of Dynamic Contrast-Enhanced MRI

Objective@#To develop a radiomics risk score based on dynamic contrast-enhanced (DCE) MRI for prognosis prediction in patients with glioblastoma. @*Materials and Methods@#One hundred and fifty patients (92 male [61.3%]; mean age ± standard deviation, 60.5 ± 13.5 years) with glioblastoma who underwent preoperative MRI were enrolled in the study. Six hundred and forty-two radiomic features were extracted from volume transfer constant (Ktrans), fractional volume of vascular plasma space (Vp), and fractional volume of extravascular extracellular space (Ve) maps of DCE MRI, wherein the regions of interest were based on both T1-weighted contrast-enhancing areas and non-enhancing T2 hyperintense areas. Using feature selection algorithms, salient radiomic features were selected from the 642 features. Next, a radiomics risk score was developed using a weighted combination of the selected features in the discovery set (n = 105); the risk score was validated in the validation set (n = 45) by investigating the difference in prognosis between the “radiomics risk score” groups. Finally, multivariable Cox regression analysis for progression-free survival was performed using the radiomics risk score and clinical variables as covariates. @*Results@#16 radiomic features obtained from non-enhancing T2 hyperintense areas were selected among the 642 features identified. The radiomics risk score was used to stratify high- and low-risk groups in both the discovery and validation sets (both p < 0.001 by the log-rank test). The radiomics risk score and presence of isocitrate dehydrogenase (IDH) mutation showed independent associations with progression-free survival in opposite directions (hazard ratio, 3.56; p = 0.004 and hazard ratio, 0.34; p = 0.022, respectively). @*Conclusion@#We developed and validated the “radiomics risk score” from the features of DCE MRI based on non-enhancing T2 hyperintense areas for risk stratification of patients with glioblastoma. It was associated with progression-free survival independently of IDH mutation status.

Cerebrovascular Reservoir and Arterial Transit Time Changes Assessed by Acetazolamide-Challenged Multi-Phase Arterial Spin Labeling Perfusion MRI in Chronic Cerebrovascular Steno-Occlusive Disease

Purpose@#To explore cerebrovascular reservoir (CVR) and arterial transit time (ATT) changes using acetazolamide-challenged multi-phase arterial spin labeling (MP-ASL) perfusion-weighted MRI in chronic cerebrovascular steno-occlusive disease. @*Materials and Methods@#This retrospective study enrolled patients with chronic steno-occlusion who underwent acetazolamide-challenged MP-ASL between June 2019 and October 2020.Cerebral blood flow, CVR, basal ATT, and ATT changes associated with severe stenosis, total occlusion, and chronic infarction lesions were compared. @*Results@#There were 32 patients (5 with bilateral steno-occlusion) in our study sample. The CVR was significantly reduced during total occlusion compared with severe stenosis (26.2% ± 28.8% vs. 41.4% ± 34.1%, respectively, p = 0.004). The ATT changes were not significantly different (p = 0.717). The CVR was marginally lower in patients with chronic infarction (29.6% ± 39.1% vs. 38.9% ± 28.7%, respectively, p = 0.076). However, the ATT was less shortened in pa-tients with chronic infarction (-54 ± 135 vs. -117 ± 128 ms, respectively, p = 0.013). @*Conclusion@#Acetazolamide-challenged MP-ASL provides an MRI-based CVR evaluation tool for chronic steno-occlusive disease.

Assessment of Mild Cognitive Impairment in Elderly Subjects Using a Fully Automated Brain Segmentation Software

Purpose@#Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD). Brain atrophy in this disease spectrum begins in the medial temporal lobe structure, which can be recognized by magnetic resonance imaging. To overcome the unsatisfactory inter-observer reliability of visual evaluation, quantitative brain volumetry has been developed and widely investigated for the diagnosis of MCI and AD. The aim of this study was to assess the prediction accuracy of quantitative brain volumetry using a fully automated segmentation software package, NeuroQuant®, for the diagnosis of MCI. @*Materials and Methods@#A total of 418 subjects from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease cohort were included in our study. Each participant was allocated to either a cognitively normal old group (n = 285) or an MCI group (n = 133). Brain volumetric data were obtained from T1-weighted images using the NeuroQuant software package. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to investigate relevant brain regions and their prediction accuracies. @*Results@#Multivariate logistic regression analysis revealed that normative percentiles of the hippocampus (P < 0.001), amygdala (P = 0.003), frontal lobe (P = 0.049), medial parietal lobe (P = 0.023), and third ventricle (P = 0.012) were independent predictive factors for MCI. In ROC analysis, normative percentiles of the hippocampus and amygdala showed fair accuracies in the diagnosis of MCI (area under the curve: 0.739 and 0.727, respectively). @*Conclusion@#Normative percentiles of the hippocampus and amygdala provided by the fully automated segmentation software could be used for screening MCI with a reasonable post-processing time. This information might help us interpret structural MRI in patients with cognitive impairment.

Ultrasonographic Indeterminate Lymph Nodes inPreoperative Thyroid Cancer Patients: Malignancy Riskand Ultrasonographic Findings Predictive of Malignancy

Objective@#Proper management of lymph nodes (LNs) with ultrasonographic (US) indeterminate features in thyroid cancerpatients remains elusive. We aimed to evaluate the malignancy risk and US findings predictive of malignancy for USindeterminate LNs in preoperative thyroid cancer patients through node-by-node correlation. @*Materials and Methods@#A total of 348 LNs in 284 thyroid cancer patients, who underwent fine-needle aspiration or coreneedlebiopsy between December 2006 and June 2015, were included. We determined the malignancy risks for US probablybenign, indeterminate, and suspicious categories. For US indeterminate LNs, which had neither echogenic hilum nor hilarvascularity in the absence of any suspicious finding, US findings were compared between benign and metastatic LNs usingMann-Whitney U test and Fisher’s exact test. @*Results@#US imaging diagnoses were probably benign in 20.7% (n = 72) cases, indeterminate in 23.6% (n = 82), andsuspicious in 55.7% (n = 194). Malignancy risk of US indeterminate LNs (19.5% [16/82]) differed from those of the USprobably benign (2.8% [2/72]) (p = 0.002) and US suspicious LNs (78.4% [152/194]) (p < 0.001). Among US indeterminate LNs,there were no significant differences in short, long, and long-to-short diameter (L/S) ratios between benign and metastatic LNs(3.9 vs. 3.8 mm, p = 0.619; 7.3 vs. 7.3 mm, p = 0.590; 1.9 vs. 1.9, p = 0.652). @*Conclusion@#US indeterminate LNs were frequently encountered during preoperative evaluation and had intermediate malignancyrisk. Given the lack of discriminative power of size criteria and L/S ratio, clinical factors such as surgical strategy and nodesize should be considered for proper triage of US indeterminate LNs in thyroid cancer.

Low-Tube-Voltage CT Urography Using Low-Concentration-Iodine Contrast Media and Iterative Reconstruction: A Multi-Institutional Randomized Controlled Trial for Comparison with Conventional CT Urography

OBJECTIVE: To compare the image quality of low-tube-voltage and low-iodine-concentration-contrast-medium (LVLC) computed tomography urography (CTU) with iterative reconstruction (IR) with that of conventional CTU. MATERIALS AND METHODS: This prospective, multi-institutional, randomized controlled trial was performed at 16 hospitals using CT scanners from various vendors. Patients were randomly assigned to the following groups: 1) the LVLC-CTU (80 kVp and 240 mgI/mL) with IR group and 2) the conventional CTU (120 kVp and 350 mgI/mL) with filtered-back projection group. The overall diagnostic acceptability, sharpness, and noise were assessed. Additionally, the mean attenuation, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and figure of merit (FOM) in the urinary tract were evaluated. RESULTS: The study included 299 patients (LVLC-CTU group: 150 patients; conventional CTU group: 149 patients). The LVLC-CTU group had a significantly lower effective radiation dose (5.73 ± 4.04 vs. 8.43 ± 4.38 mSv) compared to the conventional CTU group. LVLC-CTU showed at least standard diagnostic acceptability (score ≥ 3), but it was non-inferior when compared to conventional CTU. The mean attenuation value, mean SNR, CNR, and FOM in all pre-defined segments of the urinary tract were significantly higher in the LVLC-CTU group than in the conventional CTU group. CONCLUSION: The diagnostic acceptability and quantitative image quality of LVLC-CTU with IR are not inferior to those of conventional CTU. Additionally, LVLC-CTU with IR is beneficial because both radiation exposure and total iodine load are reduced.

The diagnostic ability of an additional midline peripheral zone biopsy in transrectal ultrasonography-guided 12-core prostate biopsy to detect midline prostate cancer

PURPOSE: The goal of this study was to evaluate the diagnostic effect of adding a midline peripheral zone (PZ) biopsy to the 12-core biopsy protocol used to diagnose prostate cancer (PC), and to assess the clinical and pathologic characteristics of midline-positive PC in order to identify a potential subgroup of patients who would require midline PZ biopsy. METHODS: This study included 741 consecutive patients who underwent a transrectal ultrasonography-guided, 12-core prostate biopsy with an additional midline core biopsy between October 2012 and December 2013. We grouped patients by the presence or absence of PC and subdivided patients with PC based on the involvement of the midline core. The clinical characteristics of these groups were compared, including serum prostate-specific antigen (PSA) concentrations, PSA density, and pathological features in the biopsy specimens. RESULTS: PC was detected in 289 patients (39.0%). Among the PC patients, 66 patients (22.8%) had midline PC. No patients were diagnosed with PC based only on a midline core. The Gleason scores, number of positive cores, tumor core length, serum PSA concentrations, and PSA density were significantly higher in patients with midline-positive PC (P<0.001). Furthermore, significant cancer was more frequent in the midline-positive group (98.5% vs. 78.0%). CONCLUSION: Patients showing a positive result for PC in a midline PZ biopsy were more likely to have multiple tumors or large-volume PC with a high tumor burden. However, our data indicated that an additional midline core biopsy is unlikely to be helpful in detecting occult midline PC.

Portable high-intensity focused ultrasound system with 3D electronic steering, real-time cavitation monitoring, and 3D image reconstruction algorithms: a preclinical study in pigs

PURPOSE: The aim of this study was to evaluate the safety and accuracy of a new portable ultrasonography-guided high-intensity focused ultrasound (USg-HIFU) system with a 3-dimensional (3D) electronic steering transducer, a simultaneous ablation and imaging module, real-time cavitation monitoring, and 3D image reconstruction algorithms. METHODS: To address the accuracy of the transducer, hydrophones in a water chamber were used to assess the generation of sonic fields. An animal study was also performed in five pigs by ablating in vivo thighs by single-point sonication (n=10) or volume sonication (n=10) and ex vivo kidneys by single-point sonication (n=10). Histological and statistical analyses were performed. RESULTS: In the hydrophone study, peak voltages were detected within 1.0 mm from the targets on the y- and z-axes and within 2.0-mm intervals along the x-axis (z-axis, direction of ultrasound propagation; y- and x-axes, perpendicular to the direction of ultrasound propagation). Twenty-nine of 30 HIFU sessions successfully created ablations at the target. The in vivo porcine thigh study showed only a small discrepancy (width, 0.5-1.1 mm; length, 3.0 mm) between the planning ultrasonograms and the pathological specimens. Inordinate thermal damage was not observed in the adjacent tissues or sonic pathways in the in vivo thigh and ex vivo kidney studies. CONCLUSION: Our study suggests that this new USg-HIFU system may be a safe and accurate technique for ablating soft tissues and encapsulated organs.