Blood Oxygen Level-Dependent MR Imaging of Lower Extremities in Peripheral Artery Disease and Its Correlation With Walking Performance.

BACKGROUND: A noninvasive and reliable approach to quantitatively measure muscle perfusion of lower extremity is needed to aid the diagnosis and treatment of peripheral artery disease (PAD). PURPOSE: To verify the reproductivity of using blood oxygen level-dependent (BOLD) imaging to evaluate perfusion in lower extremities, and explore its correlation with walking performance in patients with PAD. STUDY TYPE: Prospective observational study. SUBJECTS: Seventeen patients with lower extremity PAD (mean age: 67 ± 6 years, 15 males) and eight older adults (controls). FIELD STRENGTH/SEQUENCE: Dynamic multi-echo gradient echo T2* weighted imaging at 3T. ASSESSMENT: Perfusion was analyzed in regions of interest according to muscle groups. Perfusion parameters were measured, such as minimum ischemia value (MIV), time to peak (TTP), and gradient during reactive hyperemia (Grad) by two independent users. Walking performance experiments including short physical performance battery (SPPB) and 6-minute walk were tested in patients. STATISTICAL TESTS: BOLD parameters were compared using Mann-Whitney U test and Kruskal-Wallis test. Relations between parameters and walking performance were assessed by Mann-Whitney U test and Spearman's correlation coefficient. RESULTS: Good to perfect agreement was demonstrated for all perfusion parameters of interuser reproducibility, and the interscan reproducibility of MIV, TTP, and Grad was good. The TTP of the patients was longer than that of the controls (87.85 ± 38.85 s vs. 36.54 ± 7.27 s), while the Grad of patients was smaller (0.16 ± 0.12 msec/s vs. 0.24 ± 0.11 msec/s). Among PAD patients, the MIV was significantly lower in the low SPPB subgroup (score 6-8) than in the high SPPB group (score 9-12), and the TTP was negatively correlated with 6-minute walk distance (ρ = -0.549). DATA CONCLUSION: BOLD imaging method had overall good reproducibility for the perfusion assessment of calf muscles. The perfusion parameters were different between PAD patients and controls, and were correlated with lower extremity function. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Multidelay MR Arterial Spin Labeling Perfusion Map for the Prediction of Cerebral Hyperperfusion After Carotid Endarterectomy.

BACKGROUND: Multidelay arterial spin labeling (ASL) generates time-resolved perfusion maps, which may provide sufficient and accurate hemodynamic information in carotid stenosis. PURPOSE: To use imaging markers derived from multidelay ASL magnetic resonance imaging (MRI) and to determine the optimal strategy for predicting cerebral hyperperfusion after carotid endarterectomy (CEA). STUDY TYPE: Prospective observational cohort. SUBJECTS: A total of 79 patients who underwent CEA for carotid stenosis. FIELD STRENGTH/SEQUENCE: A 3.0 T/pseudo-continuous ASL with three postlabeling delays of 1.0, 1.57, and 2.46 seconds using fast-spin echo readout. ASSESSMENT: Cerebral perfusion pressure, antegrade, and collateral flow were scored on a four-grade ordinal scale based on preoperative multidelay ASL perfusion maps. Simultaneously, quantitative hemodynamic parameters including cerebral blood flow (CBF), arterial transit time (ATT), relative CBF (rCBF) and relative ATT (rATT; ipsilateral/contralateral values) were calculated. On the CBF ratio map obtained through dividing postoperative by preoperative CBF map, regions of interest were placed covering ipsilateral middle cerebral artery territory. Three neuroradiologists conducted this procedure. Cerebral hyperperfusion was defined as a CBF ratio >2. STATISTICAL TESTS: Weighted κ values, independent sample t test, chi-square test, Mann-Whitney U-test, multivariable logistic regression analysis, receiver-operating characteristic curve analysis, and Delong test. Significance level was P < 0.05. RESULTS: Cerebral hyperperfusion was observed in 15 (19%) patients. Higher blood pressure (odd ratio [OR] = 1.08) and carotid near-occlusion (NO; OR = 7.31) were clinical risk factors for postoperative hyperperfusion. Poor ASL perfusion score (OR = 37.33), decreased CBF (OR = 0.74), prolonged ATT (OR = 1.02), lower rCBF (OR = 0.91), and higher rATT (OR = 1.12) were independent imaging predictors of hyperperfusion. ASL perfusion score exhibited the highest specificity (95.3%), while CBF exhibited the highest sensitivity (93.3%) for the prediction of hyperperfusion. When combined with ASL perfusion score, CBF and ATT, the predictive ability was significantly higher than using blood pressure and NO alone (AUC: 0.98 vs. 0.78). DATA CONCLUSIONS: Multidelay ASL can accurately predict cerebral hyperperfusion after CEA with high sensitivity and specificity. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 5.

Arterial transit artifacts on arterial spin labeling MRI can predict cerebral hyperperfusion after carotid endarterectomy: an initial study.

OBJECTIVES: To investigate whether preoperative arterial spin labeling (ASL) MRI can predict cerebral hyperperfusion after carotid endarterectomy (CEA) in patients with carotid stenosis. METHODS: Consecutive patients with carotid stenosis who underwent CEA between May 2015 and July 2021 were included. For each patient, a cerebral blood flow ratio (rCBF) map was obtained by dividing postoperative CBF with preoperative CBF images from two pseudo-continuous ASL scans. Hyperperfusion regions with rCBF > 2 were extracted and weighted with rCBF to calculate the hyperperfusion index. According to the distribution of the hyperperfusion index, patients were divided into hyperperfusion and non-hyperperfusion groups. Preoperative ASL images were scored based on the presence of arterial transit artifacts (ATAs) in 10 regions of interest corresponding to the Alberta Stroke Programme Early Computed Tomography Score methodology. The degree of stenosis and primary and secondary collaterals were evaluated to correlate with the ASL score. Logistic regression and receiver operating characteristic curve analyses were performed to assess the predictive ability of the ASL score for cerebral hyperperfusion. RESULTS: Of 86 patients included, cerebral hyperperfusion was present in 17 (19.8%) patients. Carotid near occlusion, opening of posterior communicating arteries with incomplete anterior semicircle, and leptomeningeal collaterals were associated with lower ASL scores (p < 0.05). The preoperative ASL score was an independent predictor of cerebral hyperperfusion (OR = 0.48 [95% CI [0.33-0.71]], p < 0.001) with the optimal cutoff value of 25 points (AUC = 0.98, 94.1% sensitivity, 88.4% specificity). CONCLUSIONS: Based on the presence of ATAs, ASL can non-invasively predict cerebral hyperperfusion after CEA in patients with carotid stenosis. KEY POINTS: • Carotid near occlusion, opening of posterior communicating arteries with incomplete anterior semicircle, and leptomeningeal collaterals were associated with lower ASL scores. • The ASL score performed better than the degree of stenosis, type of CoW, and leptomeningeal collaterals, as well as the combination of the three factors for the prediction of cerebral hyperperfusion. • For patients with carotid stenosis, preoperative ASL can non-invasively identify patients at high risk of cerebral hyperperfusion after carotid endarterectomy without complex post-processing steps.

Study protocol of Branch Atheromatous Disease-related stroke (BAD-study): a multicenter prospective cohort study.

BACKGROUND: As a meaningful subtype of ischemic stroke in Asians, Branch atheromatous disease (BAD)-related stroke is associated with high early neurological deterioration (END) and disability, but is understudied and without recommended therapy. The mechanism of END still remains unclear. Branch atheromatous disease-related stroke study (BAD-study) therefore aims to investigate demographic, clinical and radiological features, and prognosis of BAD-related stroke in Chinese patients. METHODS/DESIGN: BAD-study is a nationwide, multicenter, consecutive, prospective, observational cohort study enrolling patients aged 18-80 years with BAD-related stroke within 72 h after symptom onset. Initial clinical data, laboratory tests, and imaging data are collected via structured case report form, and follow-ups will be performed at 7 days, 30 days, 90 days, 6 months and 12 months after enrollment. The primary outcome is the score on modified Rankin Scale at 90-day follow-up with single-blinded assessment. Secondary outcomes include END within 7 days, and National institute of health stroke scale score, Barthel index, cerebrovascular events, major bleeding complications, and all-cause mortality during 90-day follow-up. Characteristics of penetrating and parent artery will be assessed by high-resolution magnetic resonance imaging combined with other imaging techniques. DISCUSSION: BAD-study can provide demographic, clinical, radiological, and prognostic characteristics of BAD-related stroke, and thereby potentially figure out the vascular mechanism of early neurological deterioration and optimize therapy strategy with the aid of advanced imaging technique. Baseline data and evidence will also be generated for randomized controlled trials on BAD-related stroke in the future.

A pilot study of the association between leukoaraiosis and cerebral atherosclerosis using synthetic magnetic resonance imaging.

BACKGROUND: Leukoaraiosis is a type of lesion characterized by tissue rarefaction or myelin pallor resulting from axons loss and gliosis. Synthetic magnetic resonance imaging (MRI) could yield quantitative T1, T2, proton density (PD) values of leukoaraiosis in addition to information on the volume of the lesion. PURPOSE: To investigate the feasibility of quantifying leukoaraiosis using synthetic MRI and to explore the association between leukoaraiosis and cerebral small vascular diseases and cerebral atherosclerosis. MATERIAL AND METHODS: Patients with acute ischemic stroke were enrolled in this study. All participants underwent a conventional T2-weighted image, brain volume, CUBE fluid attenuated inversion recovery, and synthetic MRI acquisition using a 3.0-T MR system. A time-of-flight magnetic resonance angiography was also obtained. We evaluated the T1, T2, PD values and leukoaraiosis volume. RESULTS: Analysis of the leukoaraiosis volume ratios demonstrated a positive association with T2 values, a negative association with T1 values, and no association with PD values. Leukoaraiosis volume ratios were independently correlated with age (P < 0.001), lacunes (P = 0.022), and cerebral microbleeds (P = 0.010). A statistical association was found between both age (P < 0.001) and lacunes (P = 0.047) and leukoaraiosis T2 values. CONCLUSION: Synthetic MRI may enhance the evaluation of leukoaraiosis, in addition to providing information on its volume. Leukoaraiosis may represent a type of cerebral small vascular disease rather than cerebral atherosclerosis and may share the same pathological mechanism as lacunes and cerebral microbleeds.

Assessment of blood supply of the external carotid artery in moyamoya disease using super-selective pseudo-continuous arterial spin labeling technique.

OBJECTIVES: To evaluate the diagnostic accuracy of super-selective pseudo-continuous arterial spin labeling (ss-pCASL) at depicting external carotid artery (ECA) perfusion territory in moyamoya disease (MMD). METHODS: In total, 103 patients with MMD who underwent both ss-pCASL and digital subtraction angiography (DSA, the reference standard) were included. There were 3, 184, and 19 normal, preoperative, and postoperative MMD hemispheres, respectively. The ss-pCASL results were interpreted by two different visual inspection criteria: presence or absence and definite or indefinite ECA perfusion territory. The performance of ss-pCASL at depiction of ECA perfusion territory was compared to that of DSA. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. The κ statistic was used to assess intermodality and inter-reader agreement. RESULTS: When interpreted as presence or absence, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ss-pCASL for depicting ECA perfusion territory were 78.3 %, 79.6 %, 92.5 %, 53.4 %, and 78.6 %, respectively, and the intermodality and inter-reader agreement were κ = 0.49 (CI: 0.43 - 0.55, p < 0.01) and 0.71 (CI: 0.66 - 0.76, p < 0.01), respectively. When interpreted as definite or indefinite, the respective values were 61.1%, 100%, 100%, 44.5%, 70.4%, κ = 0.42 (CI: 0.37 - 0.47, p < 0.01), and 0.90 (CI: 0.87 - 0.93, p < 0.01). CONCLUSION: ss-pCASL has substantial sensitivity and specificity compared with DSA for depicting the presence versus absence of ECA perfusion territory in MMD. As a noninvasive method in which no ion radiation or contrast medium is needed, ss-pCASL may potentially reduce the need for repeated DSA examination. KEY POINTS: • Super-selective pseudo-continuous arterial spin labeling (ss-pCASL) is a noninvasive vessel-selective MR technique to demonstrate perfusion territory of a single cerebral artery. • Compared with digital subtraction angiography, ss-pCASL has substantial sensitivity and specificity for depicting the perfusion territory of the external carotid artery in brain parenchyma in moyamoya disease. • ss-pCASL may potentially reduce the need for repeated DSA examination.

Quantitative T2 mapping-based tendon healing is related to the clinical outcomes during the first year after arthroscopic rotator cuff repair.

PURPOSE: The objective of this study was to determine the correlation between quantitative T2 mapping-based tendon healing and clinical outcomes during the first year after arthroscopic rotator cuff repair. METHODS: Twenty-two patients with rotator cuff tear were prospectively recruited. Serial clinical and MRI follow-up assessments were carried out at 1 month, 6 months and 12 months after surgery. Twenty healthy volunteers were involved and were examined with clinical and MRI assessments. Clinical assessments included Constant Score (CS), the American Shoulder and Elbow Surgeons (ASES), the modified University of California, Los Angles (UCLA) scores and Visual Analog Scale (VAS). The region of interest of tendon healing was defined directly over the medial suture anchor on T2 mapping. Spearman correlation coefficient was used to analyze the correlations between MRI measurements and clinical outcomes. RESULTS: All clinical scores indicated significant improvements over the postoperative observation period compared with the initial preoperative values (all P < 0.001). At 12 months, all of the patients returned to their daily life activities. The T2 values of the healing site significantly decreased over time (P < 0.001) and were comparable to those of healthy tendons at 12 months (n.s.). Additionally, the T2 values were negatively correlated with CS (r = - 0.5, P < 0.001), ASES (r = - 0.5, P < 0.001), and UCLA (r = - 0.5, P < 0.001); and positively correlated with VAS score (r = 0.4, P < 0.001). No significant correlations were found between Sugaya classification and clinical scores (all n.s.). CONCLUSIONS: With regard to tendon healing during the first follow-up year, the T2 values of the healing site decreased with the improvement of clinical outcomes over time. LEVEL OF EVIDENCE: II.

Iron Sucrose as MRI Contrast Agent in Ischemic Stroke Model.

BACKGROUND: Despite the growing concern about the safety of gadolinium-based contrast agents (GBCAs), they are still the most commonly used. Ferumoxytol, as an off-label alternative MRI contrast agent, cannot be administered by a rapid bolus for dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI). PURPOSE: To assess the feasibility of iron sucrose (IS) as a contrast agent for MR angiography (MRA) and DSC-PWI. STUDY TYPE: Prospective animal model. ANIMAL MODEL: Thirty-six normal rats (16 for MRA, 20 for biocompability tests) and 36 occlusion of the middle cerebral artery (MCAO) model rats. FIELD STRENGTH/SEQUENCE: 3.0T; head and neck angiography, using a fast spoiled gradient-recalled-echo (FSPGR) sequence and DSC-MRI using echo planar imaging(EPI) sequence. ASSESSMENT: MRA was performed on normal rats to examine the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of different doses of IS. DSC-PWI was performed on MCAO rats at 0, 24, 48, and 72 hours postreperfusion to investigate the lesion detectability of IS. Arterial spin labeling (ASL) and DSC-PWI enhanced by GBCAs were conducted on MCAO rats as controls. STATISTICAL TESTS: Kruskal-Wallis test was used to compare qualitative assessment. One-way analysis of variance (ANOVA) was used to compare the parametric data. Pearson's r values were evaluated between relative cerebral blood flow(rCBF)-ASL, rCBF-DSCIS , and rCBF obtained from DSC-PWI enhanced by GBCA. RESULTS: The mean SNR and CNR of the common carotid artery at doses of 10 mg Fe/kg of IS were comparable with the standard dose of GBCAs (SNR: 68.04 ± 12.55 vs. 67.72 ± 14.66; CNR: 23.78 ± 7.21vs. 21.63 ± 6.83). In MCAO rat models, rCBF and relative cerebral blood volume (rCBV) of ipsilateral striatum declined (0.72 ± 0.14, 0.86 ± 0.11) with prolonged relative mean transit time (rMTT) and relative time-to-peak (rTTP) (1.27 ± 0.24, 1.07 ± 0.03) following occlusion. Hyperperfusion was observed in all rats at 48 and 72 hours postreperfusion, in 4/6 rats at 24 hours postreperfusion for IS-mediated DSC-PWI. DATA CONCLUSION: IS may be an effective contrast agent for both MRA and DSC-PWI in ischemic stroke models. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1 J. Magn. Reson. Imaging 2020;52:836-849.

Brain T1ρ mapping for grading and IDH1 gene mutation detection of gliomas: a preliminary study.

INTRODUCTION: The longitudinal relaxation time in the rotating frame (T1ρ) has proved to be sensitive to metabolism and useful in application to neurodegenerative diseases. However, few literature exists on its utility in gliomas. Thus, this study was conducted to explore the performance of T1ρ mapping in tumor grading and characterization of isocitrate dehydrogenase 1 (IDH1) gene mutation status of gliomas. METHODS: Fifty-seven patients with gliomas underwent brain MRI and quantitative measurements of T1ρ and apparent diffusion coefficient (ADC) were recorded. Parameters were compared between high-grade gliomas (HGG) and low-grade gliomas (LGG) and between IDH1 mutant and wildtype groups. RESULTS: HGG showed significantly higher T1ρ values in both the solid and peritumoral edema areas compared with LGG (P < 0.001 and P = 0.005, respectively), whereas no significant differences in the two areas were found for ADC (both P > 0.05). Receiver operating characteristic (ROC) curve analysis showed that T1ρ value in the solid area achieved the highest area under the ROC curve (AUC, 0.841) in grading with a sensitivity of 80.6% and a specificity of 81.0%. In the grade II/III glioma group, multivariate logistic regression showed that both tumor frontal lobe location (odds ratio [OR] 526.608; P = 0.045) and T1ρ value of the peritumoral edema area (OR 0.863; P = 0.037) were significant predictors of IDH1 mutation. Using the combination, the diagnostic sensitivity and specificity for IDH1 mutated gliomas were 93.3% and 88.9%, respectively. CONCLUSIONS: Our study shows the feasibility of applying T1ρ mapping in assessing the histologic grade and IDH1 mutation status of gliomas.

ASL perfusion features and type of circle of Willis as imaging markers for cerebral hyperperfusion after carotid revascularization: a preliminary study.

OBJECTIVES: Cerebral hyperperfusion (CH) could be a disastrous outcome causing complication after carotid revascularization if not managed properly and timely. The aim of this study was to investigate the association between preoperative arterial spin labelling (ASL) perfusion features and circle of Willis (CoW) pattern with CH. METHODS: Forty-eight consecutive carotid stenosis patients who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS) were enrolled. All patients had single post-labelling delay (PLD) ASL, territory-ASL, and 3-dimensional time-of-flight MR angiography (3D TOF MRA) within 2 weeks before surgery and within 3 days after surgery. Spatial coefficient of variation (CoV) of cerebral blood flow (CBF), whole brain, and territory perfusion volume ratio were calculated from ASL and territory-ASL. Postoperative CoW was classified into two groups based on patency of the first segment of the anterior cerebral arteries (A1) and anterior communicating artery (AcomA). ASL perfusion features, type of CoW, and clinical characteristics were analyzed between CH group and non-CH group to identify CH risk factors. RESULTS: Higher CoV (p = 0.005) of CBF, lower whole brain perfusion volume ratio (p = 0.012), missing any of A1 or AcomA in CoW (p = 0.002 for postoperative MRA and p = 0.004 for preoperative MRA), and large artery stroke history (p = 0.028) were significantly associated with higher risk of CH. Two cases with cerebral hyperperfusion syndrome (CHS) were also discussed, and their perfusion and angiographic features were shown. CONCLUSIONS: Single-PLD ASL and MRA might be useful and non-invasive imaging tools to identify patients with higher risk of CH after carotid revascularization. KEY POINTS: • Cerebral hyperperfusion is a critical complication after carotid endarterectomy or carotid artery stenting. • ASL and MRA can be used to identify patients at higher risk of cerebral hyperperfusion • Pattern of circle of Willis, ASL perfusion features, and whole brain perfusion volume ratio are potential predicting markers for hyperperfusion after carotid revascularization.

Effective collateral circulation may indicate improved perfusion territory restoration after carotid endarterectomy.

OBJECTIVES: To investigate the relationship between the level of collateral circulation and perfusion territory normalisation after carotid endarterectomy (CEA). METHODS: This study enrolled 22 patients with severe carotid stenosis that underwent CEA and 54 volunteers without significant carotid stenosis. All patients were scanned with ASL and t-ASL within 1 month before and 1 week after CEA. Collateral circulation was assessed on preoperative ASL images based on the presence of ATA. The postoperative flow territories were considered as back to normal if they conformed to the perfusion territory map in a healthy population. Neuropsychological tests were performed on patients before and within 7 days after surgery. RESULTS: ATA-based collateral score assessed on preoperative ASL was significantly higher in the flow territory normalisation group (n=11, 50 %) after CEA (P < 0.0001). The MMSE (mean change=1.36±0.96) and MOCA (mean change=1.18±0.95) test scores showed a significant postoperative (7 days after CEA) improvement in the flow territory normalisation group [>mean differences+2SD among control (MMSE=1.35, MOCA=1.02)]. CONCLUSIONS: This study demonstrated that effective collateral flow in carotid stenosis patients was associated with normalisation of t-ASL perfusion territory after CEA. The perfusion territory normalisation group tends to have more cognitive improvement after CEA. KEY POINTS: • Evaluation of collaterals before CEA is helpful for avoiding ischaemia during clamping. • There was good agreement on ATA-based ASL collateral grading. • Perfusion territories in carotid stenosis patients are altered. • Patients have better collateral circulation with perfusion territory back to normal. • MMSE and MOCA test scores improved more in the territory normalisation group.

Evaluation of skeletal muscle microvascular perfusion of lower extremities by cardiovascular magnetic resonance arterial spin labeling, blood oxygenation level-dependent, and intravoxel incoherent motion techniques.

BACKGROUND: Noninvasive cardiovascular magnetic resonance (CMR) techniques including arterial spin labeling (ASL), blood oxygenation level-dependent (BOLD), and intravoxel incoherent motion (IVIM), are capable of measuring tissue perfusion-related parameters. We sought to evaluate and compare these three CMR techniques in characterizing skeletal muscle perfusion in lower extremities and to investigate their abilities to diagnose and assess the severity of peripheral arterial disease (PAD). METHODS: Fifteen healthy young subjects, 14 patients with PAD, and 10 age-matched healthy old subjects underwent ASL, BOLD, and IVIM CMR perfusion imaging. Healthy young and healthy old participants were subjected to a cuff-induced ischemia experiment with pressures of 20 mmHg and 40 mmHg above systolic pressure during imaging. Perfusion-related metrics, including blood flow, T2* relaxation time, perfusion fraction f, diffusion coefficient D, and pseudodiffusion coefficient D*, were measured in the anterior, lateral, soleus, and gastrocnemius muscle groups. Friedman, Mann-Whitney, Wilcoxon signed rank, and Spearman rank correlation tests were used for statistical analysis. RESULTS: In cases of significant differences determined by the Friedman test (P < 0.05), blood flow, T2*, and D values gradually decreased, while f values showed a tendency to increase in healthy subjects under cuff compression. No significant correlations were found among the ASL, BOLD, and IVIM parameters (all P > 0.05). Blood flow and T2* values showed significant positive correlations with transcutaneous oxygen pressure measurements (ρ = 0.465 and 0.522, respectively; both P ≤ 0.001), while f values showed a significant negative correlation in healthy young subjects (ρ = - 0.351; P = 0.018). T2* was independent of age in every muscle group. T2* values were significantly decreased in PAD patients compared with healthy old subjects and severe PAD patients compared with mild-to-moderate PAD patients (all P < 0.0125). Significant correlations were found between T2* and ankle-brachial index values in all muscle groups in PAD patients (ρ = 0.644-0.837; all P < 0.0125). Other imaging parameters failed to show benefits towards the diagnosis and disease severity evaluation of PAD. CONCLUSIONS: ASL, BOLD, and IVIM provide complementary information regarding tissue perfusion. Compared with ASL and IVIM, BOLD may be a more reliable technique for assessing PAD in the resting state and could thus be applied together with angiography in clinical studies as a tool to comprehensively assess microvascular and macrovascular properties in PAD patients.

Apparent diffusion coefficient measurement in glioma: Influence of region-of-interest determination methods on apparent diffusion coefficient values, interobserver variability, time efficiency, and diagnostic ability.

PURPOSE: To compare four methods of region-of-interest (ROI) placement for apparent diffusion coefficient (ADC) measurements in distinguishing low-grade gliomas (LGGs) from high-grade gliomas (HGGs). MATERIALS AND METHODS: Two independent readers measured ADC parameters using four ROI methods (single-slice [single-round, five-round and freehand] and whole-volume) on 43 patients (20 LGGs, 23 HGGs) who had undergone 3.0 Tesla diffusion-weighted imaging and time required for each method of ADC measurements was recorded. Intraclass correlation coefficients (ICCs) were used to assess interobserver variability of ADC measurements. Mean and minimum ADC values and time required were compared using paired Student's t-tests. All ADC parameters (mean/minimum ADC values of three single-slice methods, mean/minimum/standard deviation/skewness/kurtosis/the10th and 25th percentiles/median/maximum of whole-volume method) were correlated with tumor grade (low versus high) by unpaired Student's t-tests. Discriminative ability was determined by receiver operating characteristic curves. RESULTS: All ADC measurements except minimum, skewness, and kurtosis of whole-volume ROI differed significantly between LGGs and HGGs (all P < 0.05). Mean ADC value of single-round ROI had the highest effect size (0.72) and the greatest areas under the curve (0.872). Three single-slice methods had good to excellent ICCs (0.67-0.89) and the whole-volume method fair to excellent ICCs (0.32-0.96). Minimum ADC values differed significantly between whole-volume and single-round ROI (P = 0.003) and, between whole-volume and five-round ROI (P = 0.001). The whole-volume method took significantly longer than all single-slice methods (all P < 0.001). CONCLUSION: ADC measurements are influenced by ROI determination methods. Whole-volume histogram analysis did not yield better results than single-slice methods and took longer. Mean ADC value derived from single-round ROI is the most optimal parameter for differentiating LGGs from HGGs. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:722-730.

Follow-up assessment of coiled intracranial aneurysms using zTE MRA as compared with TOF MRA: a preliminary image quality study.

OBJECTIVES: To prospectively assess coiled intracranial aneurysms using a novel non-contrast enhanced zero echo time (zTE) MR angiography (MRA) method, and compare its image quality with time-of-flight (TOF) MRA, using digital subtraction angiography (DSA) as reference. METHODS: Twenty-five patients (10 males and 15 females; age 53.96 ± 12.46 years) were enrolled in this monocentric study. MRA sequences were performed 24 h before DSA. Susceptibility artefact intensity and flow signal within the parent artery were carried out using a 4-point scale. Occlusion status was assessed using the 3-grade Montreal scale. RESULTS: Scores of zTE were higher than TOF for both susceptibility artefact intensity (3.42 ± 0.64, 2.92 ± 0.63, P = 0.01) and flow signal (3.66 ± 0.95, 3.24 ± 1.24, P = 0.01). DSA revealed 17 complete occlusions, five residual neck aneurysms and two residual aneurysms. Inter-observer agreement was excellent (weighted κ: 0.89) for zTE and good (weighted κ: 0.68) for TOF. Intermodality agreement was excellent for zTE (weighted κ: 0.95) and good for TOF (weighted κ: 0.80). Correlations of both MRA sequences with DSA were high (zTE, Spearman's ρ: 0.91; TOF, Spearman's ρ: 0.81). CONCLUSIONS: zTE MRA showed promising results for follow-up assessment of coiled intracranial aneurysms and was superior to TOF MRA for visualizing the parent artery and evaluating occlusion status. KEY POINTS: • Various MRA sequences were applied for follow-up assessment of coiled intracranial aneurysms. • zTE MRA was less sensitive to susceptibility artefacts and haemodynamics. • In this monocentric study, zTE MRA was equivalent to DSA. • zTE MRA maybe an alternative to TOF MRA for follow-up assessment.

Assessment of response to anti-angiogenic targeted therapy in pulmonary metastatic renal cell carcinoma: R2* value as a predictive biomarker.

PURPOSE: To evaluate the utility of MR R2*-mapping and the optimal time-point for assessing the response of pulmonary metastatic renal cell carcinoma (mRCC) to anti-angiogenic targeted therapy (aATT). MATERIALS AND METHODS: The exploration-sample group and the validation-sample group consisted of 22 and 16 patients. The parameters of MR R2*-mapping, including the R2* value at each time-point (R2*base, R2*1cyc and R2*2cyc) and change between different time-points (R2*(1cyc-base)/base, R2*(2cyc-base)/base and R2*(2cyc-1cyc)/1cyc), were evaluated with a receiver-operating-characteristic analysis, and a cut-off value derived from the clinical outcome was applied to the Kaplan-Meier method to assess the value of R2* mapping and Response-Evaluation-Criteria in Solid Tumours (RECIST) during treatment evaluation. RESULTS: The inter-, intra-observer agreements and inter-scan consistency were excellent (p > 0.80). For the exploration-sample group, the areas under the curve for the parameters of MR R2* mapping were 0.55, 0.60, 0.83, 0.64, 0.88 and 0.83 for R2*base, R2*1cyc, R2*2cyc, R2*(1cyc-base)/base, R2*(2cyc-base)/base and R2*(2cyc-1cyc)/1cyc. For the validation-sample, R2*(2cyc-base)/base better predicted progression-free survival (p = 0.03) than RECIST and other R2* mapping parameters with a lower p value. CONCLUSION: Assessing aATT outcome based on changes in the R2* value between baseline and second treatment is more accurate than assessment at other time-points and assessment based on the RECIST. KEY POINTS: • The inter-scan consistency of R2*-mapping in pulmonary mRCC are excellent. • The intra-/inter-observer agreement of R2* mapping in pulmonary mRCC are excellent. • Using changes in R2* value between baseline/after second-treatment is better than RECIST. • The choice of baseline/after second treatment is better than other time-points.

Evaluation of the applicability of territorial arterial spin labeling in meningiomas for presurgical assessments compared with 3-dimensional time-of-flight magnetic resonance angiography.

OBJECTIVES: To prospectively evaluate the application of territorial arterial spin labelling (t-ASL) in comparison with unenhanced three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) in the identification of the feeding vasculature of meningiomas. METHODS: Thirty consecutive patients with suspected meningiomas underwent conventional MR imaging, unenhanced 3D-TOF-MRA and t-ASL scanning. Four experienced neuro-radiologists assessed the feeding vessels with different techniques separately. RESULTS: For the identification of the origin of the feeding arteries on t-ASL, the inter-observer agreement was excellent (к = 0.913), while the inter-observer agreement of 3D-TOF-MRA was good (к = 0.653). The inter-modality agreement between t-ASL and 3D-TOF-MRA for the feeding arteries was moderate (к = 0.514). All 8 patients with motor or sensory disorders proved to have meningiomas supplied completely or partially by the internal carotid arteries, while all 14 patients with meningiomas supplied by the external carotid arteries or basilar arteries didn't show any symptoms concerning motor or sensory disorders (p = 0.003). CONCLUSION: T-ASL could complement unenhanced 3D-TOF-MRA and increase accuracy in the identification of the supplying arteries of meningiomas in a safe, intuitive, non-radioactive manner. The information about feeding arteries was potentially related to patients' symptoms and pathology, making it more crucial for neurosurgeons in planning surgery as well as evaluating prognosis. KEY POINTS: • A comprehensive understanding of feeding vasculature is helpful for optimized treatment decisions. • T-ASL could identify main supplying arteries of meningiomas with excellent inter-observer agreement. • The inter-modality agreement for identification of the main feeding arteries was moderate. • Blood supply from ICAs was related to motor or sensory disorders. • High-level meningiomas were found to have double main supplying arteries.

High-Performance Upconversion Nanoprobes for Multimodal MR Imaging of Acute Ischemic Stroke.

Multimodal magnetic resonance (MR) imaging, including MR angiography (MRA) and MR perfusion (MRP), plays a critical role in the diagnosis and surveillance of acute ischemic stroke. However, these techniques are hindered by the low T1 relaxivity, short circulation time, and high leakage rate from vessels of clinical Magnevist. To address these problems, nontoxic polyethylene glycol (PEG)ylated upconversion nanoprobes (PEG-UCNPs) are synthesized and first adopted for excellent MRA and MRP imaging, featuring high diagnostic sensitivity toward acute ischemic stroke in high-resolution imaging. The investigations show that the agent possesses superior advantages over clinical Magnevist, such as much higher relaxivity, longer circulation time, and lower leakage rate, which guarantee much better imaging efficiency. Remarkably, an extremely small dosage (5 mg Gd kg(-1) ) of PEG-UCNPs provides high-resolution MRA imaging with the vascular system delineated much clearer than the Magnevist with clinical dosage as high as 108 mg Gd kg(-1) . On the other hand, the long circulation time of PEG-UCNPs enables the surveillance of the progression of ischemic stroke using MRA or MRP. Once translated, these PEG-UCNPs are expected to be a promising candidate for substituting the clinical Magnevist in MRA and MRP, which will significantly lengthen the imaging time window and improve the overall diagnostic efficiency.

Stroke assessment with intravoxel incoherent motion diffusion-weighted MRI.

Intravoxel incoherent motion (IVIM) diffusion-weighted MRI can simultaneously measure diffusion and perfusion characteristics in a non-invasive way. This study aimed to determine the potential utility of IVIM in characterizing brain diffusion and perfusion properties for clinical stroke. The multi-b-value diffusion-weighted images of 101 patients diagnosed with acute/subacute ischemic stroke were retrospectively evaluated. The diffusion coefficient D, representing the water apparent diffusivity, was obtained by fitting the diffusion data with increasing high b-values to a simple mono-exponential model. The IVIM-derived perfusion parameters, pseudodiffusion coefficient D*, vascular volume fraction f and blood flow-related parameter fD*, were calculated with the bi-exponential model. Additionally, the apparent diffusion coefficient (ADC) was fitted according to the mono-exponential model using all b-values. The diffusion parameters for the ischemic lesion and normal contralateral region were measured in each patient. Statistical analysis was performed using the paired Student t-test and Pearson correlation test. Diffusion data in both the ischemic lesion and normal contralateral region followed the IVIM bi-exponential behavior, and the IVIM model showed better goodness of fit than the mono-exponential model with lower Akaike information criterion values. The paired Student t-test revealed significant differences for all diffusion parameters (all P < 0.001) except D* (P = 0.218) between ischemic and normal areas. For all patients in both ischemic and normal regions, ADC was significantly positively correlated with D (both r = 1, both P < 0.001) and f (r = 0.541, P < 0.001; r = 0.262, P = 0.008); significant correlation was also found between ADC and fD* in the ischemic region (r = 0.254, P = 0.010). For all pixels within the region of interest from a representative subject in both ischemic and normal regions, ADC was significantly positively correlated with D (both r = 1, both P < 0.001), f (r = 0.823, P < 0.001; r = 0.652, P < 0.001) and fD* (r = 0.294, P < 0.001; r = 0.340, P < 0.001). These findings may have clinical implications for the use of IVIM imaging in the assessment and management of acute/subacute stroke patients. Copyright © 2016 John Wiley & Sons, Ltd.

Molecular threading and tunable molecular recognition on DNA origami nanostructures.

The DNA origami technology holds great promise for the assembly of nanoscopic technological devices and studies of biochemical reactions at the single-molecule level. For these, it is essential to establish well controlled attachment of functional materials to predefined sites on the DNA origami nanostructures for reliable measurements and versatile applications. However, the two-sided nature of the origami scaffold has shown limitations in this regard. We hypothesized that holes of the commonly used two-dimensional DNA origami designs are large enough for the passage of single-stranded (ss)-DNA. Sufficiently long ssDNA initially located on one side of the origami should thus be able to "thread" to the other side through the holes in the origami sheet. By using an origami sheet attached with patterned biotinylated ssDNA spacers and monitoring streptavidin binding with atomic force microscopic (AFM) imaging, we provide unambiguous evidence that the biotin ligands positioned on one side have indeed threaded through to the other side. Our finding reveals a previously overlooked critical design feature that should provide new interpretations to previous experiments and new opportunities for the construction of origami structures with new functional capabilities.