Hyperoxia-Induced ΔR1.

Background and Purpose- Acceleration of longitudinal relaxation under hyperoxic challenge (ie, hyperoxia-induced ΔR1) indicates oxygen accumulation and reflects baseline tissue oxygenation. We evaluated the feasibility of hyperoxia-induced ΔR1 for evaluating cerebral oxygenation status and degree of ischemic damage in stroke. Methods- In 24-hour transient stroke rat models (n=13), hyperoxia-induced ΔR1, ischemic severity (apparent diffusion coefficient [ADC]), vasogenic edema (R2), total and microvascular blood volume (superparamagnetic iron oxide-driven ΔR2* and ΔR2, respectively), and glucose metabolism activity (18F-fluorodeoxyglucose uptake on positron emission tomography) were measured. The distribution of these parameters according to hyperoxia-induced ΔR1 was analyzed. The partial pressure of tissue oxygen change during hyperoxic challenge was measured using fiberoptic tissue oximetry. In 4-hour stroke models (n=6), ADC and hyperoxia-induced ΔR1 was analyzed with 2,3,5-triphenyltetrazolium chloride staining being a criterion of infarction. Results- Ischemic hemisphere showed significantly higher hyperoxia-induced ΔR1 than nonischemic brain in a pattern depending on ADC. During hyperoxic challenge, ischemic hemisphere demonstrated uncontrolled increase of partial pressure of tissue oxygen, whereas contralateral hemisphere rapidly plateaued. Ischemic hemisphere also demonstrated significant correlation between hyperoxia-induced ΔR1 and R2. Hyperoxia-induced ΔR1 showed a significant negative correlation with 18F-fluorodeoxyglucose uptake. The ADC, R2, ΔR2, and 18F-fluorodeoxyglucose uptake showed a dichotomized distribution according to the hyperoxia-induced ΔR1 as their slopes and values were higher at low hyperoxia-induced ΔR1 (<50 ms-1) than at high ΔR1. In 4-hour stroke rats, the distribution of ADC according to the hyperoxia-induced ΔR1 was similar with 24-hour stroke rats. The hyperoxia-induced ΔR1 was greater in the infarct area (47±10 ms-1) than in peri-infarct area (16±4 ms-1; P<0.01). Conclusions- Hyperoxia-induced ΔR1 adequately indicates cerebral oxygenation and can be a feasible biomarker to classify the degree of ischemia-induced damage in neurovascular function and metabolism in stroke brain.

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.

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.

Dual MRI T1 and T2(*) contrast with size-controlled iron oxide nanoparticles.

Contrast-enhancing magnetic resonance mechanism, employing either positive or negative signal changes, has contrast-specific signal characteristics. Although highly sensitive, negative contrast typically decreases the resolution and spatial specificity of MRI, whereas positive contrast lacks a high contrast-to-noise ratio but offers high spatial accuracy. To overcome these individual limitations, dual-contrast acquisitions were performed using iron oxide nanoparticles and a pair of MRI acquisitions. Specifically, vascular signals in MR angiography were positively enhanced using ultrashort echo (UTE) acquisition, which provided highly resolved vessel structures with increased vessel/tissue contrast. In addition, fast low angle shot (FLASH) acquisition yielded strong negative vessel contrast, resulting in the higher number of discernible vessel branches than those obtained from the UTE method. Taken together, the high sensitivity of the negative contrast delineated ambiguous vessel regions, whereas the positive contrast effectively eliminated the false negative contrast areas (e.g., airways and bones), demonstrating the benefits of the dual-contrast method. FROM THE CLINICAL EDITOR: In this study, the MRI properties of iron oxide nanoparticles were studied in an animal model. These contrast agents are typically considered negative contrast materials, leading to signal loss on T2* weighted images, but they also have known T1 effects as well, which is lower than that of standard positive contrast agents (like gadolinium or manganese) but is still detectable. This dual property was utilized in this study, demonstrating high sensitivity of the negative contrast in delineating ambiguous vessel regions, whereas the positive contrast eliminated false negative contrast areas (areas giving rise to susceptibility effects).

Association Between Taurine Level in the Hippocampus and Major Depressive Disorder in Young Women: A Proton Magnetic Resonance Spectroscopy Study at 7T.

BACKGROUND: Major depressive disorder (MDD) is characterized by depressed mood or loss of interest or pleasure. Generally, women are twice as likely as men to have depression. Taurine, a type of amino acid, plays critical roles in neuronal generation, differentiation, arborization, and formation of synaptic connections. Importantly, it enhances proliferation and synaptogenesis in the hippocampus. When injected into animals, taurine has an antidepressant effect. However, there is no in vivo evidence to show an association between taurine concentration in the human brain and the development of MDD. METHODS: Forty-one unmedicated young women with MDD (ages 18-29) and 43 healthy control participants matched for gender and age were recruited in South Korea. Taurine concentration was measured in the hippocampus, anterior cingulate cortex, and occipital cortex of the MDD and healthy control groups using proton magnetic resonance spectroscopy at 7T. Analysis of covariance was used to examine differences in taurine concentration, adjusting for age as a covariate. RESULTS: Taurine concentration in the hippocampus was lower (F1,75 = 5.729, p = .019, Δη2 = 0.073) for the MDD group (mean [SEM] = 0.91 [0.06] mM) than for the healthy control group (1.13 [0.06] mM). There was no significant difference in taurine concentration in the anterior cingulate cortex or occipital cortex between the two groups. CONCLUSIONS: This study demonstrates that a lower level of taurine concentration in the hippocampus may be a novel characteristic of MDD.

Targeted delivery of a phosphopeptide prodrug inhibits the proliferation of a human glioma cell line.

Peptides are ideal candidates for developing therapeutics. Polo-like kinase 1 is an important regulatory protein in the cell cycle and contains a C-terminal polo-box domain, which is the hallmark of this protein family. We developed a peptide inhibitor of polo-like kinase 1 that targets its polo-box domain. This new phosphopeptide, cRGDyK-S-S-CPLHSpT, preferentially penetrates the cancer cell membrane mediated by the integrin receptor, which is expressed at high levels by cancer cells. In the present study, using high performance liquid chromatography and mass spectroscopy, we determined the stability of cRGDyK-S-S-CPLHSpT and its cleavage by glutathione under typical conditions for cell culture. We further assessed the ability of the peptide to inhibit the proliferation of the U87MG glioma cell line. The phosphorylated peptide was stable, and the disulfide bond of cRGDyK-S-S-CPLHSpT was cleaved in 50 mM glutathione. This peptide inhibited the growth of cancer cells and changed their morphology. Therefore, we conclude that the phosphopeptide shows promise as a prodrug and has a high potential to act as an anticancer agent by inhibiting polo-like kinase 1 by binding its polo-box domain. These findings indicate the therapeutic potential of PLHSpT and peptides similarly targeted to surface receptors of cancer cells and to the functional domains of regulatory proteins.

Implementation of P22 viral capsids as intravascular magnetic resonance T1 contrast conjugates via site-selective attachment of Gd(III)-chelating agents.

P22 viral capsids and ferritin protein cages are utilized as templating macromolecules to conjugate Gd(III)-chelating agent complexes, and we systematically investigates the effects of the macromolecules' size and the conjugation positions of Gd(III)-chelating agents on the magnetic resonance (MR) relaxivities and the resulting image contrasts. The relaxivity values of the Gd(III)-chelating agent-conjugated P22 viral capsids (outer diameter: 64 nm) are dramatically increased as compared to both free Gd(III)-chelating agents and Gd(III)-chelating agent-conjugated ferritins (outer diameter: 12 nm), suggesting that the large sized P22 viral capsids exhibit a much slower tumbling rate, which results in a faster T1 relaxation rate. Gd(III)-chelating agents are attached to either the interior or exterior surface of P22 viral capsids and the conjugation positions of Gd(III)-chelating agents, however, do not have a significant effect on the relaxivity values of the macromolecular conjugates. The contrast enhancement of Gd(III)-chelating agent-conjugated P22 viral capsids is confirmed by in vitro phantom imaging at a short repetition times (TR) and the potential usage of Gd(III)-chelating agent-conjugated P22 viral capsids for in vivo MR imaging is validated by visualizing a mouse's intravascular system, including the carotid, mammary arteries, the jugular vein, and the superficial vessels of the head at an isotropic resolution of 250 µm.

MDCT-based scoring system for differentiating angiomyolipoma with minimal fat from renal cell carcinoma.

BACKGROUND: Subtype-related various computed tomography (CT) features of renal cell carcinoma (RCC) are a confusing factor in differentiating angiomyolipoma with minimal fat (AMLmf) from RCC. To overcome RCC heterogeneity, a scoring system, which integrates multiple discrimitive parameters can be helpful for differentiating AMLmf from RCC. PURPOSE: To develop a MDCT-based scoring system for differentiating AMLmf from RCC. MATERIAL AND METHODS: In 407 patients with pathologically confirmed 48 AMLmfs and 359 RCCs (247 clear cell RCCs, 67 papillary RCCs, and 45 chromophobe RCCs), MDCT features (ratio of long-to-short diameter, enhancement characteristics, tumor attenuation on unenhanced scan, tumor margin, calcification), age, and sex were compared between AMLmf and RCCs. Based on logistic regression, a scoring system for diagnosing AMLmf over RCC was built, and its diagnostic accuracy was evaluated. RESULTS: Scores suggesting AMLmf, i.e. the logit function as used in logistic regression analysis, were calculated as follows: Score = e(6.16.A-0.003.B+1.20.C+0.97.D+2.13.E-0.05.F)/1+e(6.16.A-0.003.B+1.20.C+0.97.D+2.13.E-0.05.F), where A = ratio of long-to-short diameter, B = enhancement amount in early excretory phase, C = homogeneous enhancement, D = tumor attenuation on unenhanced scan, E = sex, and F = age. Area under receiver-operating characteristics curve of scoring system was 0.919. With a score of 0.204 or higher, the scoring system yielded greatest accuracy (90%, 368/407) for diagnosing AMLmf over RCC, which was greater than that of any single MDCT or clinical parameter (53-85%) (P < 0.05). With a score of 0.317 or higher, sensitivity and specificity were 68% (32/48) and 95% (340/359). CONCLUSION: MDCT-based scoring system can improve diagnostic performance of MDCT in differentiating AMLmf from RCC and help patients with AMLmf to avoid unnecessary surgery with high specificity.

Attenuated facial movement in depressed women is associated with symptom severity, and nucleus accumbens functional connectivity.

It is assumed that mood can be inferred from one's facial expression. While this association may prove to be an objective marker for mood disorders, few studies have explicitly evaluated this linkage. The facial movement responses of women with major depressive disorder (n = 66) and healthy controls (n = 46) under emotional stimuli were recorded using webcam. To boost facial movements, the naturalistic audio-visual stimuli were presented. To assess consistent global patterns across facial movements, scores for facial action units were extracted and projected onto principal component using principal component analysis. The associations of component for facial movements with functional brain circuitry was also investigated. Clusters of mouth movements, such as lip press and stretch, identified by principal component analysis, were attenuated in depressive patients compared to those in healthy controls. This component of facial movements was associated with depressive symptoms, and the strengths of resting brain functional connectivity between nucleus accumbens and both posterior insular cortex and thalamus. The evaluation of facial movements may prove to be a promising quantitative marker for assessing depressive symptoms and their underlying brain circuitry.

Sex differences in amygdala subregions: evidence from subregional shape analysis.

Each subregion of the amygdala is characterized by a distinct cytoarchitecture and function. However, most previous studies on sexual dimorphism and aging have assessed differences in the structure of the amygdala at the level of the amygdala in its entirety rather than at the subregional level. Using an amygdala subregional shape analysis, we investigated the effects of sex, age, and the sex × age interaction on the subregion after controlling for intracranial volume. We found the main effect of age in the subregions and the effect of sex in the superficial nucleus, which showed that men had a larger mean radius than women. We also found a sex × age interaction in the centromedial nucleus, in that the radius of the centromedial nucleus showed a steeper decline with age in women compared with men. Regarding the amygdala volume as a whole, we found only an age effect and did not find any other significant difference between genders. The sex difference in the amygdala subregion and its relevance to the circulating gonadal hormone were discussed.

Evaluation of MRI resolution affecting trabecular bone parameters: determination of acceptable resolution.

The objective of this study is to evaluate the effect of MR image resolution on trabecular bone parameters and to determine the acceptable resolution that can be accurately analyzed to assess structural parameters. Ten distal femoral condyle specimens of 1 × 1 × 1 cm(3) were scanned with a 4.7-T Bruker BioSpec MRI scanner using a three-dimensional fast large-angle spin-echo sequence with various iso-cubic voxels sizes (65, 130, 160, 196, 230, and 260 µm). Otsu thresholding was applied to identify voxels containing bone. Conventional bone parameters, structural bone parameters, and skeleton-based local trabecular thickness (slTB.Th) were evaluated. The Bland-Altman method and correlation indicated that the conventional and structural bone parameters were preserved with an iso-cubic voxel size up to 230 µm (r > 0.932 and r > 0.843, respectively). In addition, slTB.Th derived from the highest resolution images (65 µm iso-cubic voxel size), correlated well (r > 0.833) with the values computed from lower resolution images, up to 230 µm, which is twice typical human trabecular thickness range (100-150 µm). The outcome of this study suggests that the various bone parameters were well preserved up to 230 µm images.

Is apparent diffusion coefficient reliable and accurate for monitoring effects of antiangiogenic treatment in a longitudinal study?

PURPOSE: To evaluate the reliability and accuracy of the apparent diffusion coefficient (ADC) for monitoring antiangiogenic treatment in a longitudinal study. MATERIALS AND METHODS: Tumor volume and ADC were monitored by T2-weighted magnetic resonance imaging (MRI) and diffusion-weighted MRI, respectively, in 18 mice with angiogenesis-dependent tumors (U118MG) before (day 0) and after 2, 7, 14, and 21 days of administration of the antiangiogenic agent sunitinib maleate (n = 12) or vehicle (n = 6). Percent changes in tumor volume and ADC were calculated and correlations between tumor volume and ADC were evaluated. RESULTS: Tumor volume and ADC showed a negative correlation at 69 of the 72 (96%) follow-up measurements. In the 13 mice with tumor regrowth, ADC started to decrease before (27%) or at the same time (73%) as tumor regrowth. Pretreatment ADC and percent change in ADC change on days 0-2 were similar in mice with positive and negative responses to treatment (0.851 vs. 0.999, 24% vs. 16%). Percent change of ADC showed significant negative correlation with percent change in tumor volume in both the control (r = -0.69) and treated (r = -0.65) groups. CONCLUSION: Percent change in ADC is a reliable and accurate marker for monitoring the effects of antiangiogenic treatment, whereas pretreatment ADC and early changes in ADC (ie, days 0-2) are limited in predicting treatment outcome.

Prostate cancer detection on dynamic contrast-enhanced MRI: computer-aided diagnosis versus single perfusion parameter maps.

OBJECTIVE: The purpose of this article is to assess the value of computer-aided diagnosis (CAD) for prostate cancer detection on dynamic contrast-enhanced MRI (DCE-MRI). MATERIALS AND METHODS: DCE-MRI examinations of 42 patients with prostate cancer were used to generate perfusion parameters, including baseline and peak signal intensities, initial slope, maximum slope within the initial 50 seconds after the contrast injection (slope(50)), wash-in rate, washout rate, time to peak, percentage of relative enhancement, percentage enhancement ratio, time of arrival, efflux rate constant from the extravascular extracellular space to the blood plasma (k(ep)), first-order rate constant for eliminating gadopentetate dimeglumine from the blood plasma (k(el)), and constant depending on the properties of the tissue and represented by the size of the extravascular extracellular space (A(H)). CAD for cancer detection was established by comprehensive evaluation of parameters using a support vector machine. The diagnostic accuracy of single perfusion parameters was estimated using receiver operating characteristic analysis, which determined threshold and parametric maps for cancer detection. The diagnostic performance of CAD for cancer detection was compared with those of T2-weighted imaging (T2WI) and single perfusion parameter maps, using histologic results as the reference standard. RESULTS: The accuracy, sensitivity, and specificity of CAD were 83%, 77%, and 77%, respectively, in the entire prostate; 77%, 91%, and 64%, respectively, in the transitional zone; and 89%, 89%, and 89%, respectively, in the peripheral zone. Values for k(ep), k(el), initial slope, slope(50), wash-in rate, washout rate, and time to peak showed greater area under the curve values (0.803-0.888) than did the other parameters (0.545-0.665) (p < 0.01) and were compared with values for CAD. In the entire prostate, accuracy was greater for CAD than for all perfusion parameters or T2WI (63-77%); sensitivity was greater for CAD than for T2WI, initial slope, wash-in rate, slope(50), and washout rate (38-77%); and specificity was greater for CAD than for T2WI, k(ep), k(el), and time to peak (59-68%) (p < 0.05). CONCLUSION: CAD can improve the diagnostic performance of DCE-MRI in prostate cancer detection, which may vary according to zonal anatomy.

Diagnosis of lymph node metastasis in uterine cervical cancer: usefulness of computer-aided diagnosis with comprehensive evaluation of MR images and clinical findings.

BACKGROUND: Lymph node (LN) status is an important parameter for determining the treatment strategy and for predicting the prognosis for patients with uterine cervical cancer. Computer-aided diagnosis (CAD) can be feasible for differentiating metastatic from non-metastatic lymph nodes in patients with uterine cervical cancer. PURPOSE: To determine the usefulness of CAD that comprehensively evaluates MR images and clinical findings for detecting LN metastasis in uterine cervical cancer. MATERIAL AND METHODS: In 680 LNs from 143 patients who underwent radical hysterectomy for uterine cervical cancer, the CAD system using the Bayesian classifier estimated the probability of metastasis based on MR findings and clinical findings. We compared the diagnostic accuracy for detecting metastatic LNs in the CAD and MR findings. RESULTS: Metastasis was diagnosed in 70 (12%) LNs from 34 (24%) patients. The area under ROC curves of CAD (0.924) was greater than those of the mean ADC (0.854), minimum ADC (0.849), maximum ADC (0.827), short-axis diameter (0.856) and long-axis diameter (0.753) (P < 0.05). The specificity and accuracy of the CAD (86%, 86%) were greater than those of the mean ADC (77%, 77%), maximum ADC (77%, 77%), minimum ADC (68%, 70%), and short-axis diameter (65%, 67%) (P < 0.05). CONCLUSION: CAD system can improve the diagnostic performance of MR for detecting metastatic LNs in uterine cervical cancer.

Feasibility of FAIR imaging for evaluating tumor perfusion.

PURPOSE: To evaluate the feasibility of flow-sensitive alternating inversion recovery (FAIR) for measuring blood flow in tumor models. MATERIALS AND METHODS: In eight mice tumor models, FAIR and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed. The reliability for measuring blood flow on FAIR was evaluated using the coefficient of variation of blood flow on psoas muscle. Three regions of interest (ROIs) were drawn in the peripheral, intermediate, and central portions within each tumor. The location of ROI was the same on FAIR and DCE-MR images. The correlation between the blood flow on FAIR and perfusion-related parameters on DCE-MRI was evaluated using the Pearson correlation coefficient. RESULTS: The coefficient of variation for measuring blood flow was 9.8%. Blood flow on FAIR showed a strong correlation with Kep (r = 0.77), percent relative enhancement (r = 0.73), and percent enhancement ratio (r = 0.81). The mean values of blood flow (mL/100 g/min) (358 vs. 207), Kep (sec(-) (1)) (7.46 vs. 1.31), percent relative enhancement (179% vs. 134%), and percent enhancement ratio (42% vs. 26%) were greater in the peripheral portion than in the central portion (P < 0.01). CONCLUSION: As blood flow measurement on FAIR is reliable and closely related with that on DCE-MR, FAIR is feasible for measuring tumor blood flow.

Node-by-node correlation between MR and PET/CT in patients with uterine cervical cancer: diffusion-weighted imaging versus size-based criteria on T2WI.

The purpose of the study was to perform a node-by-node comparison of an ADC-based diagnosis and various size-based criteria on T2-weighted imaging (T2WI) with regard to their correlation with PET/CT findings in patients with uterine cervical cancer. In 163 patients with 339 pelvic lymph nodes (LNs) with short-axis diameter >5 mm, the minimum apparent diffusion coefficient (ADC), mean ADC, short- and long-axis diameters, and ratio of long- to short-axis diameters (L/S ratio) were compared in PET/CT-positive and -negative LNs. On PET/CT, 118 (35%) LNs in 58 patients were positive. The mean value of minimum and mean ADCs, short- and long-axis diameters, and L/S ratio were different in PET/CT-positive (0.6436 x 10(-3) mm(2)/s, 0.756 x 10(-3) mm(2)/s, 10.3 mm, 13.2 mm, 1.32, respectively) and PET/CT-negative LNs (0.8893 x 10(-3) mm(2)/s, 1.019 x 10(-3) mm(2)/s, 7.4 mm, 11.0 mm, 1.49, respectively) (P < 0.05). The Az value of the minimum ADC (0.864) was greater than those of mean ADC (0.836), short-axis diameter (0.764), long-axis diameter (0.640) and L/S ratio (0.652) (P < 0.05). The sensitivity and accuracy of the minimum ADC (86%, 82%) were greater than those of the short-axis diameter (55%, 74%), long-axis diameter (73%, 58%) and L/S ratio (52%, 66%) (P < 0.05). ADC showed superior correlation with PET/CT compared with conventional size-based criteria on T2WI.

Spatiotemporal heterogeneity of tumor vasculature during tumor growth and antiangiogenic treatment: MRI assessment using permeability and blood volume parameters.

Tumor heterogeneity is an important concept when assessing intratumoral variety in vascular phenotypes and responses to antiangiogenic treatment. This study explored spatiotemporal heterogeneity of vascular alterations in C6 glioma mice during tumor growth and antiangiogenic treatment on serial MR examinations (days 0, 4, and 7 from initiation of vehicle or multireceptor tyrosine kinase inhibitor administration). Transvascular permeability (TP) was quantified on dynamic-contrast-enhanced MRI (DCE-MRI) using extravascular extracellular agent (Gd-DOTA); blood volume (BV) was estimated using intravascular T2 agent (SPION). With regard to region-dependent variability in vascular phenotypes, the control group demonstrated higher TP in the tumor center than in the periphery, and greater BV in the tumor periphery than in the center. This distribution pattern became more apparent with tumor growth. Antiangiogenic treatment effect was regionally heterogeneous: in the tumor center, treatment significantly suppressed the increase in TP and decrease in BV (ie, typical temporal change in the control group); in the tumor periphery, treatment-induced vascular alterations were insignificant and BV remained high. On histopathological examination, the control group showed greater CD31, VEGFR2, Ki67, and NG2 expression in the tumor periphery than in the center. After treatment, CD31 and Ki67 expression was significantly suppressed only in the tumor center, whereas VEGFR2 and α-caspase 3 expression was decreased and NG2 expression was increased in the entire tumor. These results demonstrate that MRI can reliably depict spatial heterogeneity in tumor vascular phenotypes and antiangiogenic treatment effects. Preserved angiogenic activity (high BV on MRI and high CD31) and proliferation (high Ki67) in the tumor periphery after treatment may provide insights into the mechanism of tumor resistance to antiangiogenic treatment.

Reduced microvascular volume and hemispherically deficient vasoreactivity to hypercapnia in acute ischemia: MRI study using permanent middle cerebral artery occlusion rat model.

Vasoreactivity to hypercapnia has been used for assessing cerebrovascular tone and control altered by ischemic stroke. Despite the high prognostic potential, traits of hypercapnia-induced hemodynamic changes have not been fully characterized in relation with baseline vascular states and brain tissue damage. To monitor cerebrovascular responses, T2- and T2*-weighted magnetic resonance imaging (MRI) images were acquired alternatively using spin- and gradient-echo echo plannar imaging (GESE EPI) sequence with 5% CO2 gas inhalation in normal (n=5) and acute stroke rats (n=10). Dynamic relative changes in cerebrovascular volume (CBV), microvascular volume (MVV), and vascular size index (VSI) were assessed from regions of interest (ROIs) delineated by the percent decrease of apparent diffusion coefficient (ADC). The baseline CBV was not affected by middle cerebral artery occlusion (MCAO) whereas the baseline MVV in ischemic areas was significantly lower than that in the rest of the brain and correlated with ADC. Vasoreactivity to hypercapnic challenge was considerably attenuated in the entire ipsilesional hemisphere including normal ADC regions, in which unsolicited, spreading depression-associated increases of CBV and MVV were observed. The lesion-dependent inhomogeneity in baseline MVV indicates the effective perfusion reserve for accurately delineating the true ischemic damage while the cascade of neuronal depolarization is probably responsible for the hemispherically lateralized changes in overall neurovascular physiology.

Nuclear magnetic resonance-compatible furnace for high temperature MR imaging and spectroscopy in situ.

A high temperature magnetic resonance compatible furnace for real time in situ monitoring of materials, processes, and chemical reactions with magnetic resonance imaging and spectroscopy is described. Design issues are analyzed. Example applications are demonstrated with a time sequence of proton images of the binder burnout in a porous green ceramic cylinder containing polyethylene glycol binder at 200 degrees C, and 7Li images of the molten salt LiCl at 700 degrees C.

Response of the primary auditory and non-auditory cortices to acoustic stimulation: a manganese-enhanced MRI study.

Structural and functional features of various cerebral cortices have been extensively explored in neuroscience research. We used manganese-enhanced MRI, a non-invasive method for examining stimulus-dependent activity in the whole brain, to investigate the activity in the layers of primary cortices and sensory, such as auditory and olfactory, pathways under acoustic stimulation. Male Sprague-Dawley rats, either with or without exposure to auditory stimulation, were scanned before and 24-29 hour after systemic MnCl2 injection. Cortex linearization and layer-dependent signal extraction were subsequently performed for detecting layer-specific cortical activity. We found stimulus-dependent activity in the deep layers of the primary auditory cortex and the auditory pathways. The primary sensory and visual cortices also showed the enhanced activity, whereas the olfactory pathways did not. Further, we performed correlation analysis of the signal intensity ratios among different layers of each cortex, and compared the strength of correlations between with and without the auditory stimulation. In the primary auditory cortex, the correlation strength between left and right hemisphere showed a slight but not significant increase with the acoustic simulation, whereas, in the primary sensory and visual cortex, the correlation coefficients were significantly smaller. These results suggest the possibility that even though the primary auditory, sensory, and visual cortices showed enhanced activity to the auditory stimulation, these cortices had different associations for auditory processing in the brain network.