A radiomics based method for prediction of prostate cancer Gleason score using enlarged region of interest.

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers in men worldwide, and its timely diagnosis and treatment are becoming increasingly important. MRI is in increasing use to diagnose cancer and to distinguish between non-clinically significant and clinically significant PCa, leading to more precise diagnosis and treatment. The purpose of this study is to present a radiomics-based method for determining the Gleason score (GS) for PCa using tumour heterogeneity on multiparametric MRI (mp-MRI). METHODS: Twenty-six patients with biopsy-proven PCa were included in this study. The quantitative T2 values, apparent diffusion coefficient (ADC) and signal enhancement rates (α) were calculated using multi-echo T2 images, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI), for the annotated region of interests (ROI). After texture feature analysis, ROI range expansion and feature filtering was performed. Then obtained data were put into support vector machine (SVM), K-Nearest Neighbor (KNN) and other classifiers for binary classification. RESULTS: The highest classification accuracy was 73.96% for distinguishing between clinically significant (Gleason 3 + 4 and above) and non-significant cancers (Gleason 3 + 3) and 83.72% for distinguishing between Gleason 3 + 4 from Gleason 4 + 3 and above, which was achieved using initial ROIs drawn by the radiologists. The accuracy improved when using expanded ROIs to 80.67% using SVM and 88.42% using Bayesian classification for distinguishing between clinically significant and non-significant cancers and Gleason 3 + 4 from Gleason 4 + 3 and above, respectively. CONCLUSIONS: Our results indicate the research significance and value of this study for determining the GS for prostate cancer using the expansion of the ROI region.

Directional and inter-acquisition variability in diffusion-weighted imaging and editing for restricted diffusion.

PURPOSE: To evaluate and quantify inter-directional and inter-acquisition variation in diffusion-weighted imaging (DWI) and emphasize signals that report restricted diffusion to enhance cancer conspicuity, while reducing the effects of local microscopic motion and magnetic field fluctuations. METHODS: Ten patients with biopsy-proven prostate cancer were studied under an Institutional Review Board-approved protocol. Individual acquisitions of DWI signal intensities were reconstructed to calculate inter-acquisition distributions and their statistics, which were compared for healthy versus cancer tissue. A method was proposed to detect and filter the acquisitions affected by motion-induced signal loss. First, signals that reflect restricted diffusion were separated from the acquisitions that suffer from signal loss, likely due to microscopic motion, by imposing a cutoff value. Furthermore, corrected apparent diffusion coefficient maps were calculated by employing a weighted sum of the multiple acquisitions, instead of conventional averaging. These weights were calculated by applying a soft-max function to the set of acquisitions per-voxel, making the analysis immune to acquisitions with significant signal loss, even if the number of such acquisitions is high. RESULTS: Inter-acquisition variation is much larger than the Rician noise variance, local spatial variations, and the estimates of diffusion anisotropy based on the current data, as well as the published values of anisotropy. The proposed method increases the contrast for cancers and yields a sensitivity of 98 . 8 % $$ 98.8\% $$ with a false positive rate of 3 . 9 % $$ 3.9\% $$ . CONCLUSION: Motion-induced signal loss makes conventional signal-averaging suboptimal and can obscure signals from areas with restricted diffusion. Filtering or weighting individual acquisitions prior to image analysis can overcome this problem.

The optimal 18F-fluoromisonidazole PET threshold to define tumor hypoxia in preclinical squamous cell carcinomas using pO2 electron paramagnetic resonance imaging as reference truth.

PURPOSE: To identify the optimal threshold in 18F-fluoromisonidazole (FMISO) PET images to accurately locate tumor hypoxia by using electron paramagnetic resonance imaging (pO2 EPRI) as ground truth for hypoxia, defined by pO2 [Formula: see text] 10 mmHg. METHODS: Tumor hypoxia images in mouse models of SCCVII squamous cell carcinoma (n = 16) were acquired in a hybrid PET/EPRI imaging system 2 h post-injection of FMISO. T2-weighted MRI was used to delineate tumor and muscle tissue. Dynamic contrast enhanced (DCE) MRI parametric images of Ktrans and ve were generated to model tumor vascular properties. Images from PET/EPR/MRI were co-registered and resampled to isotropic 0.5 mm voxel resolution for analysis. PET images were converted to standardized uptake value (SUV) and tumor-to-muscle ratio (TMR) units. FMISO uptake thresholds were evaluated using receiver operating characteristic (ROC) curve analysis to find the optimal FMISO threshold and unit with maximum overall hypoxia similarity (OHS) with pO2 EPRI, where OHS = 1 shows perfect overlap and OHS = 0 shows no overlap. The means of dice similarity coefficient, normalized Hausdorff distance, and accuracy were used to define the OHS. Monotonic relationships between EPRI/PET/DCE-MRI were evaluated with the Spearman correlation coefficient ([Formula: see text]) to quantify association of vasculature on hypoxia imaged with both FMISO PET and pO2 EPRI. RESULTS: FMISO PET thresholds to define hypoxia with maximum OHS (both OHS = 0.728 [Formula: see text] 0.2) were SUV [Formula: see text] 1.4 [Formula: see text] SUVmean and SUV [Formula: see text] 0.6 [Formula: see text] SUVmax. Weak-to-moderate correlations (|[Formula: see text]|< 0.70) were observed between PET/EPRI hypoxia images with vascular permeability (Ktrans) or fractional extracellular-extravascular space (ve) from DCE-MRI. CONCLUSION: This is the first in vivo comparison of FMISO uptake with pO2 EPRI to identify the optimal FMISO threshold to define tumor hypoxia, which may successfully direct hypoxic tumor boosts in patients, thereby enhancing tumor control.

Quick evaluation of lower leg ischemia in patients with peripheral arterial disease by time maximum intensity projection CT angiography: a pilot study.

BACKGROUND: The purpose of this study is to evaluate a new method involving time maximum intensity projection (t-MIP) postprocessed from dynamic computed tomographic angiography (dyn-CTA) in diagnosing peripheral arterial disease (PAD). METHODS: A population of 34 patients with known PAD was examined with a combined CTA protocol consisting of a standard CTA (s-CTA) scan of the lower extremities and a dyn-CTA scan of the calves. For each lower leg, t-MIP images consisting of the MIP0 (sagittal MIP), MIP+θ (45° lateral MIP), and MIP-θ (- 45° lateral MIP) were automatically generated from dyn-CTA. An objective evaluation of the vascular CT attenuation of the best enhancement phase of dyn-CTA and t-MIP was measured; a subjective evaluation of vessel stenosis and occlusion was performed, assigning a score for t-MIP and s-CTA. The CT attenuation of t-MIP and dyn-CTA was compared, as were the runoff scores of t-MIP and s-CTA. RESULTS: The CT attenuation of t-MIP CTA of three vascular segments from 68 lower extremities was higher than that of the best enhancement phase of dyn-CTA and s-CTA, with statistically significant differences at the posterior tibial artery and fibular artery (all p < 0.05). There were strong correlations (r ≥ 0.75, p < 0.05) of the runoff scores between t-MIP and s-CTA. CONCLUSIONS: There is potential clinical applicability of t-MIP in assisting with the diagnosis of lower leg vascular stenosis in dyn-CTA with reliable diagnostic accuracy and convenient immediacy.

Magnetic resonance angiography reveals increased arterial blood supply and tumorigenesis following high fat feeding in a mouse model of triple-negative breast cancer.

Breast cancer is the second most commonly diagnosed malignancy among women globally. Past MRI studies have linked a high animal fat diet (HAFD) to increased mammary cancer risk in the SV40Tag mouse model of triple-negative breast cancer. Here, serial MRI examines tumor progression and measures the arterial blood volume feeding mammary glands in low fat diet (LFD) or HAFD fed mice. Virgin female C3(1)SV40Tag mice (n = 8), weaned at 3 weeks old, were assigned to an LFD (n = 4, 3.7 kcal/g, 17.2% kcal from vegetable oil) or an HAFD (n = 4, 5.3 kcal/g, 60% kcal from lard) group. From ages 8 to 12 weeks, weekly fast spin echo MR images and time-of-flight (TOF) MR angiography of inguinal mammary glands were acquired at 9.4 T. Following in vivo MRI, mice were sacrificed. Inguinal mammary glands were excised and fixed for ex vivo MRI and histology. Tumor, blood, and mammary gland volumes for each time point were measured from manually traced regions of interest; tumors were classified as invasive by histopathology-blinded observers. Our analysis confirmed a strong correlation between total tumor volume and blood volume in the mammary gland. Tumor growth rates from weeks 8-12 were twice as high in HAFD-fed mice (0.42 ± 0.14/week) as in LFD-fed mice (0.21 ± 0.03/week), p < 0.004. Mammary gland blood volume growth rate was 2.2 times higher in HAFD mice (0.29 ± 0.11/week) compared with LFD mice (0.13 ± 0.06/week), p < 0.02. The mammary gland growth rate of HAFD-fed mice (0.071 ± 0.011/week) was 2.7 times larger than that of LFD-fed mice (0.026 ± 0.009/week), p < 0.01. This is the first non-invasive, in vivo MRI study to demonstrate a strong correlation between an HAFD and increased cancer burden and blood volume in mammary cancer without using contrast agents, strengthening the evidence supporting the adverse effects of an HAFD on mammary cancer. These results support the potential future use of TOF angiography to evaluate vasculature of suspicious lesions.

Quantitative Analysis of Lower Leg Muscle Enhancement Measured From Dynamic Computed Tomographic Angiography for Diagnosis of Peripheral Arterial Occlusive Disease.

OBJECTIVES: The purpose of this study was to evaluate whether quantitative analysis of lower leg muscle enhancement measured from dynamic computed tomographic angiography (dyn-CTA) could be used for diagnosis of peripheral arterial occlusive disease. METHODS: Patients (N = 35) with known peripheral arterial occlusive disease underwent the dyn-CTA of calves first. Five minutes later, standard CTA of the peripheral runoff from the diaphragm to the toes was performed. A runoff score was assigned by radiologists as a reference standard for each of 4 lower leg artery segments. The lower leg muscle enhancement measured from the dyn-CTA was analyzed by using quantitative kinetic parameters, including initial enhancement (E1), peak enhancement (Epeak), and enhancement ratio (ER) calculated from average time attenuation curves. In addition, histogram of lower leg muscle enhancement was evaluated by using the first enhanced phase images. RESULTS: Lower extremities were diagnosed as a normal group (n = 22) with each vessel segment score equals to 1 or lower and runoff score, 7 or lower, and otherwise as an ischemia group (n = 48). Average ± SD E1 is 91.4% ± 8.5% and 82.3% ± 10.7%, Epeak is 122.7% ± 10.4% and 115.6% ± 11.1%, and ER is 0.75 ± 0.05 and 0.72 ± 0.09 for normal and ischemia group, respectively. Statistical analysis showed that average E1 and Epeak for the ischemia group were significantly lower (P < 0.05) than the normal group. The histogram analysis demonstrated that mean and median of muscle enhancement in the ischemia group were significantly smaller (P < 0.05), and coefficient of variation (CV) was significantly larger (P < 0.05) than the normal group. There were weak negative correlations (r = -0.42, P < 0.05) between runoff scores and E1 and Epeak, and weak positive correlation (r = 0.40, P < 0.05) between runoff scores and CV. The receiver operating characteristics analysis between the 2 groups had area under the curve of 0.77 and 0.76 for E1 and CV, respectively. CONCLUSIONS: Lower leg muscle enhancement measured from the dyn-CTA could be assessed quantitatively to assist diagnosis of ischemia in clinical practice.

Evaluation of Focal Laser Ablation of Prostate Cancer Using High Spectral and Spatial Resolution Imaging: A Pilot Study.

BACKGROUND: Focal laser ablation (FLA) is a minimally invasive thermal ablation, guided by MRI through an optical fiber, to induce coagulative necrosis in cancer. PURPOSE: To evaluate the feasibility of high spectral and spatial resolution imaging using multiecho gradient echo (MEGE) MRI for identification of ablation zones, after FLA of prostate cancers. STUDY TYPE: Prospective. POPULATION: Fourteen patients with biopsy-confirmed localized prostate cancers. FIELD STRENGTH/SEQUENCE: FLA was performed under monitored conscious sedation with a 1.5T MRI scanner. Axial MEGE images were acquired before and after the last FLA. Pre- and postcontrast enhanced T1 -weighted (pT1 W) images were acquired to assess the FLA zone as a reference standard. ASSESSMENT: The T 2 * maps and water resonance peak height (WPH) images were calculated from the MEGE data. Ablation area was outlined using an active contour method. The maximum ablation area and total ablation volume were calculated from T 2 * and WPH images, and compared with the sizes measured from pT1 W images. STATISTICAL TESTS: Nonparametric Kruskal-Wallis tests were performed to determine whether there was significant difference in calculated ablation areas and volumes between T 2 * , WPH, and pT1 W images. RESULTS: Average T 2 * (38.9 ± 14.1 msec) in the ablation area was significantly shorter (P = 0.03) than the preablation area T 2 * (57.8 ± 25.3 msec). The normalized WPH value over the ablation area (1.3 ± 0.6) was significantly decreased (P = 0.02) more than the preablation area (2.0 ± 0.9). The maximum ablation areas measured by T 2 * (295.7 ± 96.4 mm2 ), WPH (312.2 ± 63.0 mm2 ), and pT1 W (320.3 ± 82.9 mm2 ) images were all similar. Furthermore, there was no significant difference (P = 0.31) for measured ablation volumes 3310.5 ± 649.5, 3406.4 ± 684.9, and 3672.5 ± 832.4 mm3 between T 2 * , WPH, and pT1 W images, respectively. DATA CONCLUSION: T 2 * and WPH images provide acceptable measurements of ablation zones during FLA treatment of prostate cancers without the need for contrast agent injection. This might allow repeated assessment following each heating period so that subsequent ablations can be optimized. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;49:1374-1380.

Safety of Intra-Arterial Tirofiban Administration in Ischemic Stroke Patients after Unsuccessful Mechanical Thrombectomy.

PURPOSE: To assess the safety of low-dose intra-arterial (IA) tirofiban bolus after unsuccessful mechanical thrombectomy in patients with ischemic stroke due to large artery occlusion in anterior cerebral circulation. MATERIALS AND METHODS: Patients with ischemic stroke who were treated with mechanical thrombectomy were enrolled in a multicenter registry. Low-dose tirofiban was injected into the residual arterial thrombus in patients after unsuccessful mechanical thrombectomy. The major safety measurement was defined as symptomatic intracranial hemorrhage (SICH). The functional outcome at 90 days was assessed with the modified Rankin Scale, and a score of 0-2 was defined as favorable. RESULTS: Of the 632 enrolled patients, 154 (24.4%) received IA tirofiban treatment. The SICH rate was 13.6% (21/154) in patients with tirofiban and 16.7% (80/478) in patients without tirofiban (P = .361). IA tirofiban was not associated with increased risk of SICH (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.36-1.31; P = .26). IA tirofiban treatment did not increase the risk of mortality at 90 days of the index stroke (OR, 0.66; 95% CI, 0.36-1.31; P = .15). Patients with large artery atherosclerosis stroke who were treated with tirofiban were associated with decreased risk of death (OR, 11.3% vs 23.4%; P = .042) compared to patients who were not treated with tirofiban. CONCLUSIONS: Low-dose IA tirofiban administration may be relatively safe in patients with ischemic stroke after unsuccessful recanalization.

Diagnosis of Prostate Cancer by Use of MRI-Derived Quantitative Risk Maps: A Feasibility Study.

OBJECTIVE. The purpose of this study was to develop a new quantitative image analysis tool for estimating the risk of cancer of the prostate by use of quantitative multiparametric MRI (mpMRI) metrics. MATERIALS AND METHODS. Thirty patients with biopsy-confirmed prostate cancer (PCa) who underwent preoperative 3-T mpMRI were included in the study. Quantitative mpMRI metrics-apparent diffusion coefficient (ADC), T2, and dynamic contrast-enhanced (DCE) signal enhancement rate (α)-were calculated on a voxel-by-voxel basis for the whole prostate and coregistered. A normalized risk value (0-100) for each mpMRI parameter was obtained, with high risk values associated with low T2 and ADC and high signal enhancement rate. The final risk score was calculated as a weighted sum of the risk scores (ADC, 40%; T2, 40%; DCE, 20%). Data from five patients were used as training set to find the threshold for predicting PCa. In the other 25 patients, any region with a minimum of 30 con-joint voxels (≈ 4.8 mm2) with final risk score above the threshold was considered positive for cancer. Lesion-based and sector-based analyses were performed by matching prostatectomyverified malignancy and PCa predicted with the risk analysis tool. RESULTS. The risk map tool had sensitivity of 76.6%, 89.2%, and 100% for detecting all lesions, clinically significant lesions (≥ Gleason 3 + 4), and index lesions, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for PCa detection for all lesions in the sector-based analysis were 78.9%, 88.5%, 84.4%, and 84.1%, respectively, with an ROC AUC of 0.84. CONCLUSION. The risk analysis tool is effective for detecting clinically significant PCa with reasonable sensitivity and specificity in both peripheral and transition zones.

MRI Findings After MRI-Guided Focal Laser Ablation of Prostate Cancer.

OBJECTIVE: The purpose of this study is to describe the quantitative and qualitative findings of multiparametric prostate MRI performed after MRI-guided focal laser ablation of prostate cancer. MATERIALS AND METHODS: A total of 27 consenting patients met the study inclusion criteria, which included but were not limited to the presence of clinical category T1c-T2a prostate cancer with a Gleason score of 7 or less, having undergone prostate biopsy before and after focal laser ablation, and having undergone MRI before ablation, immediately after ablation, and 3 and 12 months after ablation. Signal changes were evaluated both qualitatively and quantitatively and were then correlated with the results of subsequent biopsy performed at 3 and 12 months after ablation. RESULTS: MRI performed immediately after ablation revealed a hypovascular defect in the ablation zone, with patchy or bandlike decreased T2 signal most commonly noted at 3 months (in 66.7% of ablated lesions) and T2 scarring observed in most lesions (66.7%) at 12 months. Patchy or bandlike decreased apparent diffusion coefficient signal and scarlike changes were most prevalent at 3 months after ablation (50.0% of lesions), and these features remained the most commonly observed findings at 12 months after ablation (27.8% of lesions). At 12 months after ablation, 10 patients were found to have recurrent tumor, with three patients found to have persistent cancer when biopsy was performed at the ablation site. All postablation biopsy cases with positive results showed suspicious T2 and apparent diffusion coefficient characteristics, which were considered to be a well-defined nodular intermediate signal on both of these sequences. Two of the patients for whom positive biopsy findings were noted had focal enhancement of the ablation zone. A significant reduction in the forward volume transfer constant after ablation was found at the ablation site on follow-up examination. CONCLUSION: Multiparametric MRI can reveal postablation changes in the prostate and can be a valuable tool for monitoring patients who have undergone MRI-guided focal laser ablation.

MRI reveals increased tumorigenesis following high fat feeding in a mouse model of triple-negative breast cancer.

High animal fat consumption is associated with an increase in triple-negative breast cancer (TNBC) risk. Based on previous MRI studies demonstrating the feasibility of detecting very early non-palpable mammary cancers in simian virus 40 large T antigen (SV40TAg) mice, we examined the effect of dietary fat fed from weaning to young adulthood in this model of TNBC. Virgin female C3(1)SV40TAg mice (n = 16) were weaned at 3-4 weeks of age and then fed either a low fat diet (LFD) (n = 8, 3.7 kcal/g; 17.2% kcal from vegetable oil) or a high animal fat diet (HAFD) (n = 8, 5.3 kcal/g; 60% kcal from lard). After 8 weeks on the diet (12 weeks of age), fast spin echo MR images of inguinal mammary glands were acquired at 9.4 T. Following in vivo MRI, mice were sacrificed and inguinal mammary glands were excised and formalin fixed for ex vivo MRI. 3D volume-rendered MR images were then correlated with mammary gland histology to assess the glandular parenchyma and tumor burden. Using in vivo MRI, an average of 3.88 ± 1.03 tumors were detected per HAFD-fed mouse compared with an average of 1.25 ± 1.16 per LFD-fed mouse (p < 0.007). Additionally, the average tumor volume was significantly higher following HAFD feeding (0.53 ± 0.45 mm3 ) compared with LFD feeding (0.20 ± 0.08 mm3 , p < 0.02). Analysis of ex vivo MR and histology images demonstrated that HAFD mouse mammary glands had denser parenchyma, irregular and enlarged ducts, dilated blood vessels, increased white adipose tissue, and increased tumor invasion. MRI and histological studies of the SV40TAg mice demonstrated that HAFD feeding also resulted in higher cancer incidence and larger mammary tumors. Unlike other imaging methods for assessing environmental effects on mammary cancer growth, MRI allows routine serial measurements and reliable detection of small cancers as well as accurate tumor volume measurements and assessment of the three-dimensional distribution of tumors over time.

Comparison of central hemodynamic parameters for young basketball athletes and control group.

BACKGROUND: Long-term exercise training may have negative effects on cardiovascular functions. Measurement and calculation of central hemodynamic parameters can comprehensively evaluate the cardiovascular functions. This study aims to compare the central hemodynamics between young basketball athletes and matched controls. METHODS: Total 19 young long-term trained male basketball athletes and 17 matched male recreationally active controls participated. The central hemodynamic parameters such as central blood pressure, pulse pressure, heart rate (HR), augmentation index normalised to 75 bpm (AIx@HR75), augmentation index (AIx), ejection duration (ED), sub-endocardial viability ratio (SEVR) were measured, and total peripheral resistance (TPR), stroke volume (SV) and cardiac output (CO) were calculated. Non-parameter tests and t-test were used to analyse the central hemodynamic parameters between athletes and controls. RESULTS: HR (56 ± 5 bpm versus 79 ± 9 bpm, p < .001), AIx@HR75 (-8 ± 10% versus -1 ± 10%, p < .05), ED (28 ± 2% versus 36 ± 3%, p < .001) and TPR (0.004 ± 0.006 mmHg s/mL versus 0.012 ± 0.006 mmHg s/mL, p < .001) were significantly lower in basketball athletes compared to the controls. SEVR (231 ± 32% versus 159 ± 21%, p < .001) and SV (154 ± 50 mL versus 101 ± 43 mL, p < .01) were significantly higher in basketball athletes than those in the controls. However, there were no significant differences in central blood pressure, pulse pressure, AIx and CO between them. CONCLUSIONS: There is no negative effect on central hemodynamics in young basketball athletes after long-term exercise training. The young basketball athletes have a higher myocardial perfusion, higher efficiency of blood supply, stronger vascular functions and better balance of myocardial oxygen of supply and demand than the controls in this central hemodynamic parameters analysis.

B1 and T1 mapping of the breast with a reference tissue method.

PURPOSE: To develop a method for mapping the B1 field using a reference signal from a tissue with known T1. METHODS: Flip angle correction factors were calculated in a region with a known "gold standard" T1; by comparing T1 values from a variable flip angle (VFA) sequence to the "gold standard" and correcting the value of the Ernst angle. The resulting partial B1 map was interpolated for all other regions. In the breast, fat is an ideal reference tissue because its T1 is spatially homogeneous and interpatient variability is low. This method was tested with scans of phantoms and patients (n = 4) on a 3T magnet. The performance of the method was evaluated by comparing the results of VFA T1 mapping with and without B1 correction to inversion recovery (IR) T1 maps. RESULTS: Phantom data determined that a linear inverse distance weighted interpolation accurately recovered the full B1 map. Use of interpolated maps to correct the VFA data in vivo, reduced the average difference in the T1 of parenchyma between VFA and IR results from 58% to 8%. CONCLUSION: This proof-of-principle study showed that it is possible to recover a full and accurate map of the B1 field in the breast by using a reference tissue (fat) with an accurately measured T1.

Quantitative Multiparametric MRI Features and PTEN Expression of Peripheral Zone Prostate Cancer: A Pilot Study.

OBJECTIVE: The objective of our study was to investigate associations between quantitative image features of multiparametric MRI of the prostate and PTEN expression of peripheral zone prostate cancer. MATERIALS AND METHODS: A total of 45 peripheral zone cancer foci from 30 patients who had undergone multiparametric prostate MRI before prostatectomy were identified by a genitourinary pathologist and a radiologist who reviewed histologic findings and MR images. Histologic sections of cancer foci underwent immunohistochemical analysis and were scored according to the percentage of tumor-positive cells expressing PTEN as negative (0-20%), mixed (20-80%), or positive (80-100%). Average and 10th percentile apparent diffusion coefficient (ADC) values, skewness of T2-weighted signal intensity histogram, and quantitative perfusion parameters (i.e., forward volume transfer constant [K(trans)], extravascular extracellular volume fraction [ve], and reverse reflux rate constant between the extracellular space and plasma [k(ep)]) from the Tofts model were calculated for each cancer focus. Associations between the quantitative image features and PTEN expression were analyzed with the Spearman rank correlation coefficient (r). RESULTS: Analysis of the 45 cancer foci revealed that 21 (47%) were PTEN-positive, 12 (27%) were PTEN-negative, and 12 (27%) were mixed. There was a weak but significant negative correlation between Gleason score and PTEN expression (r = -0.30, p = 0.04) and between k(ep) and PTEN expression (r = -0.35, p = 0.02). There was no significant correlation between other multiparametric MRI features and PTEN expression. CONCLUSION: This preliminary study of radiogenomics of peripheral zone prostate cancer revealed weak-but significant-associations between the quantitative dynamic contrast-enhanced MRI feature k(ep) and Gleason score with PTEN expression. These findings warrant further investigation and validation with the aim of using multiparametric MRI to improve risk assessment of patients with prostate cancer.

Impact of chromosome 12p13 variants on ischemic stroke risk.

BACKGROUND: In 2009, a genome-wide association study (GWAS) identified two variants (rs12425791 and rs11833579) near NINJ2 gene that confer susceptibility to stroke in Caucasian populations. Recently, a number of studies have been conducted to replicate this finding in Asian populations. However, the results are conflicting. Thus, we performed a quantitative analysis to summarize the evidence regarding the association between these two polymorphisms and ischemic stroke risk. METHODS: Pertinent studies were identified by searching PubMed and Embase through September 2014. Studies that reported odds ratio (OR) with 95% confidence interval (CI) for the association between these two polymorphisms and stroke risk were included. RESULTS: Eight independent publications, with 8626 cases and 8046 controls for rs12425791 and 9142 cases and 8657 controls for rs11833579, were included. Overall, significantly increased ischemic stroke risk was associated with rs12425791 A allele when all studies were pooled into the meta-analysis (AA/GA vs. GG: OR = 1.08, 95% CI: 1.01-1.14). However, rs11833579 was not associated with increased stroke risk in any genetic model. CONCLUSIONS: These findings indicate that rs12425791 G>A polymorphism may be a low-penetrance susceptibility marker of stroke in Asian populations and further studies are warranted to verify this association.

MRI accurately identifies early murine mammary cancers and reliably differentiates between in situ and invasive cancer: correlation of MRI with histology.

MRI methods that accurately identify various stages of mouse mammary cancer could provide new knowledge that may have a direct impact on the management of breast cancer in patients. This research investigates whether we can accurately follow the progression from in situ to invasive cancer by the evaluation of in vivo and ex vivo MRI, and in comparison with histology as the gold standard for the diagnosis and staging of cancer. Six C3(1)SV40Tag virgin female mice, aged 12-16 weeks, were studied. At this age, these mice develop in situ cancer that resembles human ductal carcinoma in situ (DCIS). Fast spin-echo images of inguinal mammary glands were acquired at 9.4 T. After in vivo MRI, mice were sacrificed; inguinal mammary glands were excised and fixed in formalin for ex vivo MRI. Three-dimensional, volume-rendered, in vivo and ex vivo MR images were then correlated with histology. High-resolution ex vivo scans facilitated the comparison of in vivo scans with histology. The sizes of mammary cancers classified as in situ on the basis of histology ranged from 150 to 400 µm in largest diameter, and the average signal intensity relative to muscle was 1.40 ± 0.18 on T2 -weighted images. Cancers classified as invasive on the basis of histology were >400 µm in largest diameter, and the average intensity relative to muscle on T2 -weighted images was 2.34 ± 0.26. Using a cut-off of 400 µm in largest diameter to distinguish between in situ and invasive cancers, a T2 -weighted signal intensity of at least 1.4 times that of muscle for in situ cancer, and at least 2.3 times that of muscle for invasive cancer, 96% of in situ and 100% of invasive cancers were correctly identified on in vivo MRI, using histology as the gold standard. Precise MRI-histology correlation demonstrates that MRI reliably detects early in situ cancer and differentiates in situ from invasive cancers in the SV40Tag mouse model of human breast cancer.

Multiple intracranial arterial stenosis influences the long-term prognosis of symptomatic middle cerebral artery occlusion.

BACKGROUND: Large intracranial occlusive vascular disease is a major contributor to the incidence of stroke worldwide, especially when it involves the middle cerebral artery (MCA). The data on the prognosis of symptomatic atherosclerotic MCA occlusions (MCAO) with concomitant intracranial arterial disease (MCAO-AIS) are limited. MCAO-AIS may reflect the extent of the atherosclerotic intracranial disease, we hypotheses that coexisting intracranial arterial disease influenced the prognosis of MCAO. METHODS: Patients having survived at least one month after the initial ischemic stroke who suffered from atherosclerotic occlusion of the MCA were enrolled. According to their concomitant atherosclerotic intracranial arterial disease, the patients were assigned to one of two groups: the MCAO or the MCAO-AIS. All of the patients' cerebrovascular risk factors were recorded. Recurrent ischemic stroke and death were the end-point events during the follow-up. RESULTS: A total of 232 patients (mean age 57.68 ± 9.50 years; 69% male) were analyzed. The mean follow-up time was 17.65 months. The end-point events occurred in 35 (15.09%) patients, resulting in an annual rate of 10.26%. The presence of MCAO- AIS was an independent risk factor associated with the patient's prognosis in the cohort (OR = 3.426, 95% CI 1.261 to 9.308; p = 0.016), as well as gender and diabetes mellitus. The MCAO-AIS were more likely to experience ipsilateral ischemic strokes, but the difference was not statistically significant. CONCLUSION: Concomitant intracranial arterial disease may influence the prognosis of patients with atherosclerotic MCAO. The result warrants further research in larger sample population.

The Circle of Willis and White Matter Lesions in Patients with Carotid Atherosclerosis.

BACKGROUND: The correlation between cerebral atherosclerosis and white matter lesions (WMLs) in the elderly was controversial in the published articles, where the stenosis was often evaluated by ultrasonography, computed tomography angiography, or magnetic resonance angiography and collaterals were seldom considered. We hypothesized that collaterals influence WMLs. Our study was to explore the relationship between the circle of Willis and WMLs in a retrospective, hospital-based cohort of patients with carotid atherosclerosis. METHODS: Two hundred eighty-six patients with carotid atherosclerosis were enrolled from the Nanjing Stroke Registry. They underwent magnetic resonance imaging evaluating WMLs and digital subtraction angiography evaluating both carotid atherosclerosis and collateral capacity of the circle of Willis. We tested the association between severe carotid atherosclerosis, the circle of Willis, and WMLs by logistic regression analysis. RESULTS: Severity of carotid atherosclerosis was not significantly associated with either periventricular or deep WMLs (P = .656 and .566, respectively). Number of carotid arteries with severe stenosis was not associated with the severity of either periventricular or deep WMLs (P = .721 and .263, respectively). Patency of the communicating arteries (CoA) was not associated with periventricular or deep WMLs (P = .561 and .703, respectively). Advanced age and hypertension were associated with periventricular WMLs (P = .001 and .008, respectively). Advanced age, hypertension, and prior stroke were associated with deep WMLs (P = .049, .048, and .001, respectively). CONCLUSIONS: The circle of Willis and severe carotid atherosclerosis may not be related to WMLs. Further larger studies are warranted to confirm or refute our findings.

Mammary cancer initiation and progression studied with magnetic resonance imaging.

INTRODUCTION: Previous work from this laboratory demonstrated that magnetic resonance imaging (MRI) detects early murine mammary cancers and reliably differentiates between in situ and invasive cancer. Based on this previous work, we used MRI to study initiation and progression of murine mammary cancer, and monitor the transition from the in situ to the invasive phase. METHODS: In total, seven female C3(1) SV40 Tag mice were imaged every two weeks between the ages of 8 to 23 weeks. Lesions were identified on T2-weighted images acquired at 9.4 Tesla based on their morphology and growth rates. Lesions were traced manually on MR images of each slice. Volume of each lesion was calculated by adding measurements from individual slices. Plots of lesion volume versus time were analyzed to obtain the specific growth rate (SGR). The time at which in situ cancers (referred to as 'mammary intraepithelial neoplasia (MIN)') and invasive cancers were first detected; and the time at which in situ cancers became invasive were recorded. RESULTS: A total of 121 cancers (14 to 25 per mouse) were identified in seven mice. On average the MIN lesions and invasive cancers were first detected when mice were 13 and 18 weeks old, respectively. The average SGR was 0.47 ± 0.18 week(-1) and there were no differences (P >0.05) between mice. 74 lesions had significantly different tumor growth rates before and after ~17 weeks of age; with average doubling times (DT) of 1.88 and 1.27 weeks, respectively. The average DT was significantly shorter (P <0.0001) after 17 weeks of age. However, the DT for some cancers was longer after 17 weeks of age, and about 10% of the cancers detected did not progress to the invasive stage. CONCLUSIONS: A wide range of growth rates were observed in SV40 mammary cancers. Most cancers transitioned to a more aggressive phenotype at approximately 17 weeks of age, but some cancers became less aggressive. The results suggest that the biology of mammary cancers is extremely heterogeneous. This work is a first step towards use of MRI to improve understanding of factors that control and/or signal the development of aggressive breast cancer.

Blood-brain barrier permeable gold nanoparticles: an efficient delivery platform for enhanced malignant glioma therapy and imaging.

The blood-brain barrier (BBB) remains a formidable obstacle in medicine, preventing efficient penetration of chemotherapeutic and diagnostic agents to malignant gliomas. Here, a transactivator of transcription (TAT) peptide-modified gold nanoparticle platform (TAT-Au NP) with a 5 nm core size is demonstrated to be capable of crossing the BBB efficiently and delivering cargoes such as the anticancer drug doxorubicin (Dox) and Gd(3+) contrast agents to brain tumor tissues. Treatment of mice bearing intracranial glioma xenografts with pH-sensitive Dox-conjugated TAT-Au NPs via a single intravenous administration leads to significant survival benefit when compared to the free Dox. Furthermore, it is demonstrated that TAT-Au NPs are capable of delivering Gd(3+) chelates for enhanced brain tumor imaging with a prolonged retention time of Gd(3+) when compared to the free Gd(3+) chelates. Collectively, these results show promising applications of the TAT-Au NPs for enhanced malignant brain tumor therapy and non-invasive imaging.