Hyperoxia-Induced ΔR1: MRI Biomarker of Histological Infarction in Acute Cerebral Stroke.

OBJECTIVE: To evaluate whether hyperoxia-induced ΔR1 (hyperO2ΔR1) can accurately identify histological infarction in an acute cerebral stroke model. MATERIALS AND METHODS: In 18 rats, MRI parameters, including hyperO2ΔR1, apparent diffusion coefficient (ADC), cerebral blood flow and volume, and 18F-fluorodeoxyglucose uptake on PET were measured 2.5, 4.5, and 6.5 hours after a 60-minutes occlusion of the right middle cerebral artery. Histological examination of the brain was performed immediately following the imaging studies. MRI and PET images were co-registered with digitized histological images. The ipsilateral hemisphere was divided into histological infarct (histological cell death), non-infarct ischemic (no cell death but ADC decrease), and non-ischemic (no cell death or ADC decrease) areas for comparisons of imaging parameters. The levels of hyperO2ΔR1 and ADC were measured voxel-wise from the infarct core to the non-ischemic region. The correlation between areas of hyperO2ΔR1-derived infarction and histological cell death was evaluated. RESULTS: HyperO2ΔR1 increased only in the infarct area (p ≤ 0.046) compared to the other areas. ADC decreased stepwise from non-ischemic to infarct areas (p = 0.002 at all time points). The other parameters did not show consistent differences among the three areas across the three time points. HyperO2ΔR1 sharply declined from the core to the border of the infarct areas, whereas there was no change within the non-infarct areas. A hyperO2ΔR1 value of 0.04 s-1 was considered the criterion to identify histological infarction. ADC increased gradually from the infarct core to the periphery, without a pronounced difference at the border between the infarct and non-infarct areas. Areas of hyperO2ΔR1 higher than 0.04 s-1 on MRI were strongly positively correlated with histological cell death (r = 0.862; p < 0.001). CONCLUSION: HyperO2ΔR1 may be used as an accurate and early (2.5 hours after onset) indicator of histological infarction in acute stroke.

Amide proton transfer-weighted MRI can detect tissue acidosis and monitor recovery in a transient middle cerebral artery occlusion model compared with a permanent occlusion model in rats.

OBJECTIVES: To assess whether increases in amide proton transfer (APT)-weighted signal reflect the effects of tissue recovery from acidosis using transient rat middle cerebral artery occlusion (MCAO) models, compared to permanent occlusion models. MATERIALS AND METHODS: Twenty-four rats with MCAO (17 transient and seven permanent occlusions) were prepared. APT-weighted signal (APTw), apparent diffusion coefficient (ADC), cerebral blood flow (CBF), and MR spectroscopy were evaluated at three stages in each group (occlusion, reperfusion/1 h post-occlusion, and 3 h post-reperfusion/4 h post-occlusion). Deficit areas showing 30% reduction to the contralateral side were measured. Temporal changes were compared with repeated measures of analysis of variance. Relationship between APTw and lactate concentration was calculated. RESULTS: Both APTw and CBF values increased and APTw deficit area reduced at reperfusion (largest p = .002) in transient occlusion models, but this was not demonstrated in permanent occlusion. No significant temporal change was demonstrated with ADC at reperfusion. APTw deficit area was between ADC and CBF deficit areas in transient occlusion model. APTw correlated with lactate concentration at occlusion (r = - 0.49, p = .04) and reperfusion (r = - 0.32, p = .02). CONCLUSIONS: APTw values increased after reperfusion and correlated with lactate content, which suggests that APT-weighted MRI could become a useful imaging technique to reflect tissue acidosis and its reversal. KEY POINTS: • APT-weighted signal increases in the tissue reperfusion, while remains stable in the permanent occlusion. • APTw deficit area was between ADC and CBF deficit areas in transient occlusion model, possibly demonstrating metabolic penumbra. • APTw correlated with lactate concentration during ischemia and reperfusion, indicating tissue acidosis.

Simultaneous evaluation of vascular morphology, blood volume and transvascular permeability using SPION-based, dual-contrast MRI: imaging optimization and feasibility test.

Exploiting ultrashort-T(E) (UTE) MRI, T1-weighted positive contrast can be obtained from superparamagnetic iron oxide nanoparticles (SPIONs), which are widely used as a robust T2-weighted, negative contrast agent on conventional MR images. Our study was designed (a) to optimize the dual-contrast MRI method using SPIONs and (b) to validate the feasibility of simultaneously evaluating the vascular morphology, blood volume and transvascular permeability using the dual-contrast effect of SPIONs. All studies were conducted using 3 T MRI. According to numerical simulation, 0.15 mM was the optimal blood SPION concentration for visualizing the positive contrast effect using UTE MRI (T(E) = 0.09 ms), and a flip angle of 40° could provide sufficient SPION-induced enhancement and acceptable measurement noise for UTE MR angiography. A pharmacokinetic study showed that this concentration can be steadily maintained from 30 to 360 min after the injection of 29 mg/kg of SPIONs. An in vivo study using these settings displayed image quality and CNR of SPION-enhanced UTE MR angiography (image quality score 3.5; CNR 146) comparable to those of the conventional, Gd-enhanced method (image quality score 3.8; CNR 148) (p > 0.05). Using dual-contrast MR images obtained from SPION-enhanced UTE and conventional spin- and gradient-echo methods, the transvascular permeability (water exchange index 1.76-1.77), cerebral blood volume (2.58-2.60%) and vessel caliber index (3.06-3.10) could be consistently quantified (coefficient of variation less than 9.6%; Bland-Altman 95% limits of agreement 0.886-1.111) and were similar to the literature values. Therefore, using the optimized setting of combined SPION-based MRI techniques, the vascular morphology, blood volume and transvascular permeability can be comprehensively evaluated during a single session of MR examination.

Postoperative quality of life in patients with progressive neuromuscular scoliosis and their parents.

BACKGROUND CONTEXT: The functional level of children with progressive neuromuscular disease is a major factor that affects the quality of life (QOL) of parents. However, only a few publications have reported changes in the QOL of parents after correctional spinal surgery. PURPOSE: The purpose was to compare changes in QOL for both patients and parents after spinal correctional surgery for better sitting balance and to analyze correlation among radiographic parameters, functional outcome, and QOL questionnaires. Finally, the QOL of patients and parents was compared with the population norm. STUDY DESIGN: This study is a retrospective analysis of prospectively gathered data. PATIENT SAMPLE: From 2008 to 2011, 58 patients who underwent correctional surgery for progressive neuromuscular scoliosis and their parents were enrolled. OUTCOME MEASURES: A Muscular Dystrophy Spine Questionnaire (MDSQ) and short-form questionnaire 36 (SF-36) were used. METHODS: The gathered functional outcome and QOL data using MDSQ and SF-36 for both enrolled patients and parents were compared preoperatively, postoperatively at 3 months, and at 1-year follow-up. RESULTS: Mean age was 15.0±4.1 years. Forty male and 18 female patients were enrolled. Mean follow-up was 38.4±13.7 months. Cobb angle was 61.5°±23.5° preoperatively, 39.0°±20.1° immediately postoperative, and 40.0°±20.2° at the final follow-up. Cobb angle, pelvic obliquity, and lumbar lordosis were significantly improved after surgery (p<.001). Among sitting-related questions, answers to questions 15 (sitting comfortably), 16 (change weight in wheelchair), 22 (sit all day), 24 (sit at table for meal), 26 (keep balance while sitting in wheelchair), and 27 (look good while sitting in wheelchair) were significantly improved after correctional surgery (p<.001). Regarding the SF-36 scales for patients, bodily pain and social functioning significantly improved postoperatively (p<.001). CONCLUSIONS: Muscular Dystrophy Spine Questionnaire results indicated that patients had significantly improved sitting balance-related outcomes, whereas the SF-36 indicated improvements only in bodily pain and social functioning scales. For parents, no SF-36 scales improved significantly postoperatively. Accordingly, improved sitting balance and QOL for neuromuscular scoliosis patients after surgery do not necessarily increase parent QOL.

Oxygen-induced frequency shifts in hyperoxia: a significant component of BOLD signal.

In comparison to the well-documented significance of intravascular deoxyhemoglobin (deoxyHgb), the effects of dissolved oxygen on the blood-oxygen-level-dependent (BOLD) signal have not been widely reported. Based on the fact that the prolonged inspiration of high oxygen fraction gas can result in up to a sixfold increase of the baseline tissue oxygenation, the current study focused on the influence of dissolved oxygen on the BOLD signal during hyperoxia. As results, our in vitro study revealed that the r1 and r2 (relaxivities) of the oxygen-treated serum were 0.22 mM(-1) · s(-1) and 0.19 mM(-1) · s(-1) , respectively. In an in vivo experiment, hyperoxic respiration induced negative BOLD contrast (i.e. signal decrease) in 18-42% of measured brain regions, voxels with accompanying significant decreases in both the T(*)2 (-12.1% to -19.4%) and T1 (-5.8% to -3.3%) relaxation times. In contrast, the T(*)2 relaxation time significantly increased (11.2% to 14.0%) for the voxels displaying positive BOLD contrast (in 41-50% of the measured brain), which reflected a hyperoxygenation-induced reduction in tissue deoxyHgb concentration. These data imply that hyperoxia-driven BOLD signal changes are primarily determined by the counteracting effects of extravascular oxygen and intravascular deoxyHgb. Oxygen-induced magnetic susceptibility was further demonstrated by the study of 1 min hypoxia, which induced BOLD signal changes opposite to those under hyperoxia. Vasoconstriction was more common in voxels with negative BOLD contrast than in voxels with positive contrast (% change of blood volume, -9.8% to -12.8% versus 2.0% to 2.2%), which further suggests that negative BOLD contrast is mainly evoked by an increase in extravascular oxygen concentration. Conclusively, frequency shifts, which are induced by the accumulation of oxygen molecules and associated magnetic field inhomogeneity, are a significant source of the negative BOLD contrast during hyperoxia.

Sunitinib--CLIO conjugate: a VEGFR/PDGFR-targeting active MR probe.

PURPOSE: This study was conducted to evaluate feasibility of sunitinib-CLIO conjugate as a vascular endothelial growth factor receptor/platelet-derived growth factor receptor (VEGFR/PDGFR)-specific magnetic resonance (MR) probe. PROCEDURE: VEGFR/PDGFR-targeting MR probe was synthesized by conjugating cross-linked iron-oxide (CLIO) with tyrosine-kinase inhibitor (sunitinib). In VEGFR/PDGFR-positive (U118MG) and VEGFR/PDGFR-negative (HT29) cells and tumor models, conjugate-driven ΔR 2 was estimated, while CLIO was used as control. Prussian-blue staining was performed for quantifying the amount of tumor-binding conjugates. RESULTS: ΔR 2 between sunitinib-CLIO-treated and non-treated cells was greater in U118MG (mean, 2.1/s) than in HT29 cells (1.0/s). In in vivo study, conjugate induced a greater ΔR 2 in U118MG (11.2/s) than HT29 tumors (5.9/s). Conjugate-induced R 2 changes were not correlated with degree of Gd-DTPA enhancement, demonstrating that tumor binding of sunitinib-CLIO was independent of enhanced permeability and retention effect. % area of Prussian-blue staining was greater in U118MG (8.5 %) than in HT29 (1.4 %). CONCLUSIONS: Sunitinib-CLIO conjugate can be used as an active MR probe for quantifying VEGFR/PDGFR.