Lipo-prostaglandin E1 improves renal hypoxia evaluated by BOLD-MRI in patients with diabetic kidney disease.

OBJECTIVE: To evaluate the effect of lipo-PGE1 on renal hypoxia in patients with DKD by BOLD-MRI. MATERIALS AND METHODS: All patients were divided into DKD group and CKD-without-diabetes group. All patients received intravenous 10 µg lipo-PGE1 once daily for 14 days. BOLD-MRI was performed before and after lipo-PGE1 administration to acquire renal CR2* and MR2* values. RESULTS: Renal MR2* value in DKD group after lipo-PGE1 treatment were significantly decreased compared with the baseline. However, no significant differences in MR2* values were found in the CKD-without-diabetes group. CONCLUSIONS: Lipo-PGE1 was shown to improve kidney medullary oxygenation in patients with DKD.

Diagnostic value of renal perfusion in patients with chronic kidney disease using 3D arterial spin labeling.

PURPOSE: To evaluate the diagnostic value of 3D arterial spin labeling (ASL) for noninvasive quantification of renal blood flow (RBF) in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: CKD patients (n = 27) and healthy volunteers (n = 36) underwent renal 3T ASL magnetic resonance imaging, with inversion times from 1200 to 2000 msec for volunteers in the preliminary test, and 1800 to 2000 msec for volunteers and CKD patients in the formal experiments. The cortical RBFs were compared, and a correlation between RBF and estimated glomerular filtration rate (eGFR) was evaluated. RESULTS: For healthy volunteers, RBF values increased with TIs from 1200 to 1600 msec, but were almost constant at TIs from 1600 to 2000 msec. The cortical RBF values of CKD patients were lower than that of healthy volunteers at TIs from 1800 to 2000 msec. In addition, the CKD patients had lower cortical RBF values than the healthy volunteers (P < 0.01 for both), and their RBF values positively correlated with eGFR. CONCLUSION: 3D ASL is a potential noninvasive method for measuring renal perfusion that can provide valuable information for clinical CKD diagnosis. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;46:589-594.

Readout-segmented echo-planar imaging improves the image quality of diffusion-weighted MR imaging in rectal cancer: Comparison with single-shot echo-planar diffusion-weighted sequences.

PURPOSE: To determine whether readout-segmented echo-planar imaging (rs-EPI) diffusion-weighted imaging (DWI) can improve the image quality in patients with rectal cancer compared with single-shot echo-planar imaging (ss-EPI) DWI using 3.0 T magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the Institutional Review Board, and informed consent was obtained from all patients. Seventy-one patients with rectal cancer were enrolled in this study. For all patients, both rs-EPI and ss-EPI DWI were performed using a 3T MR scanner. Two radiologists independently assessed the overall image quality, lesion conspicuity, geometric distortion and distinction of anatomical structures. The signal-to-noise ratio (SNR), lesion contrast, contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) were also measured. Comparisons of the quantitative and qualitative parameters between the two sequences were performed using the paired t-test and the Wilcoxon signed rank test. RESULTS: The scores of overall image quality, lesion conspicuity, geometric distortion and distinction of anatomical structures of rs-EPI were all significantly higher than those of ss-EPI (all p<0.05). The SNR and CNR were higher in rs-EPI than those in ss-EPI (all p<0.05). There was no significant difference between ss-EPI and rs-EPI with regard to ROI size and mean ADCs of the tumour (p=0.574 and p=0.479, respectively), but the mean ADC of the normal tissue was higher in rs-EPI than in ss-EPI (1.73±0.30×10(-3)mm(2)/s vs. 1.60±0.31×10(-3)mm(2)/s, p=0.001). CONCLUSIONS: DW imaging based on readout-segmented echo-planar imaging is a clinically useful technique to improve the image quality for the purpose of evaluating lesions in patients with rectal tumours.

[Chemical Exchange Saturation Transfer Imaging of Creatine Metabolites: a 3.0 T MRI Pilot].

OBJECTIVE: To determine the feasibility of using chemical exchange saturation transfer (CEST) imaging to measure creatine (Cr) metabolites with 3.0 T MR. METHODS: Phantoms containing different concentrations of Cr under various pH conditions were studied with CEST sequence on 3.0 T MR imaging. CEST effect and Z spectra were analyzed. RESULTS: Cr exhibited significant CEST effect (± 1.8 ppm, F = 99.08, P < 0.001) on 3.0 T MR imaging, and positive correlation was found between the signal intensity and concentration of Cr (r = 0.963, P < 0.001). The CEST effect showed pH dependency of Cr (r = 0.41, P = 0.035). CONCLUSION: Creatine CEST imaging can be performed on 3.0 T MR imaging. Creatine concentrations and pH influence CEST effect.

SEMAC-VAT MR Imaging Unravels Peri-instrumentation Lesions in Patients With Attendant Symptoms After Spinal Surgery.

The study aimed for evaluating the diagnostic value of a 2D Turbo Spin Echo (TSE) magnetic resonance (MR) imaging sequence implanted slice-encoding metal artifact correction (SEMAC) and view-angle tilting (VAT) in patients with spinal instrumentation.Sixty-seven consecutive patients with an average age of 59.7 ±â€Š17.8 years old (range: 32-75 years) were enrolled in this study. Both sagittal, axial T1-weighted and T2-weighted MRI images were acquired with a standard TSE sequence and a high-bandwidth TSE sequence implemented the SEMAC and VAT techniques. Three continuous sections around the instrumentation in axial and sagittal images were selected for quantitative evaluation. The measurement included cumulative areas of signal void on axial images and the length of spinal canal obscuration on sagittal images. Three radiologists independently evaluated all images blindly. The inter-observer reliability was evaluated with inter-class coefficient. We defined patients with discomfortable symptoms caused by spinal instrumentation as spinal instrumentation adverse reaction.Visualizations of all periprosthetic anatomic structures were significantly better for SEMAC-VAT compared with standard imaging. For axial images, the area of signal void at the level of the instrumentation were statistically reduced with SEMAC-VAT TSE sequences than with standard TSE sequences for T2-weighted images (9.9 ±â€Š2.6 cm vs 29.8 ±â€Š14.7 cm, P < 0.001). For sagittal imaging, the length of spinal canal obscuration at the level of the instrumentation was reduced from 5.2 ±â€Š2.0 cm to 1.2 ±â€Š0.6 cm on T2-weighted images (P < 0.001), and from 4.8 ±â€Š2.1 cm to 1.1 ±â€Š0.5 cm on T1-weighted images with SEMAC-VAT sequences (P < 0.001). Interobserver agreement for visualization of anatomic structures and image quality was good for both SEMAC-VAT (k = 0.77 and 0.68, respectively) and standard (k = 0.74 and 0.80, respectively) imaging. The number of abnormal findings noted on SEMAC images (59 findings) was significantly higher than detected on standard images (40 findings). The incidence rate of spinal instrumentation adverse reaction was 38.81%.MR images with SEMAC-VAT can significantly reduce metal artifacts for spinal instrumentation and improve delineation of the instrumentation and periprosthetic region. Furthermore, SEMAC-VAT technique can improve diagnostic accuracy in patients with post-instrumentation spinal diseases.

Evaluation of renal allografts function early after transplantation using intravoxel incoherent motion and arterial spin labeling MRI.

PURPOSE: To evaluate renal allografts function early after transplantation using intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) MRI. METHODS: This prospective study was approved by the local ethics committee, and written informed consent was obtained from all participants. A total of 82 participants with 62 renal allograft recipients (2-4weeks after kidney transplantation) and 20 volunteers were enrolled to be scanned using IVIM and ASL MRI on a 3.0T MR scanner. Recipients were divided into two groups with either normal or impaired function according to the estimated glomerular filtration rate (eGFR) with a threshold of 60ml/min/1.73m(2). The apparent diffusion coefficient (ADC) of pure diffusion (ADCslow), the ADC of pseudodiffusion (ADCfast), perfusion fraction (PF), and renal blood flow (RBF) of cortex were compared among three groups. The correlation of ADCslow, ADCfast, PF and RBF with eGFR was evaluated. The receiver operating characteristic (ROC) curve and binary logistic regression analyses were performed to assess the diagnostic efficiency of using IVIM and ASL parameters to discriminate allografts with impaired function from normal function. P<0.05 was considered statistically significant. RESULTS: In allografts with normal function, no significant difference of mean cortical ADCslow, ADCfast, and PF was found compared with healthy controls (P>0.05). Cortical RBF in allografts with normal function was statistically lower than that of healthy controls (P<0.001). Mean cortical ADCslow, ADCfast, PF and RBF were lower for allografts with impaired function than that with normal function (P<0.05). Mean cortical ADCslow, ADCfast, PF and RBF showed a positive correlation with eGFR (all P<0.01) for recipients. The combination of IVIM and ASL MRI showed a higher area under the ROC curve (AUC) (0.865) than that of ASL MRI alone (P=0.02). CONCLUSION: Combined IVIM and ASL MRI can better evaluate the diffusion and perfusion properties for allografts early after kidney transplantation.

Assessment of renal allograft function early after transplantation with isotropic resolution diffusion tensor imaging.

OBJECTIVES: To investigate the value of diffusion tensor imaging (DTI) and tractography in renal allografts at the early stage after kidney transplantation. METHODS: This study was approved by the institutional ethical review committee, and written informed consent was obtained. A total of 54 renal allograft recipients 2-3 weeks after transplantation and 26 age-matched healthy volunteers underwent renal DTI with a 3.0-T magnetic resonance imaging (MRI) system. Recipients were divided into three groups according to the estimated glomerular filtration rate (eGFR). Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the cortex and medulla were measured and compared among the groups. Whole-kidney tractography was performed. Correlation of eGFR with diffusion parameters was evaluated. RESULTS: In allografts with stable function, the medullary ADC was higher and the cortical FA was lower (p < 0.001) than in healthy kidneys. The cortical ADC, medullary ADC and FA decreased as the allograft function declined, and with a positive correlation with eGFR (p < 0.001); cortical FA did not. Tractography demonstrated a decrease of tract density in impaired functional allografts. CONCLUSIONS: Renal DTI produces reliable results to assess renal allograft function at the early stage after transplantation. KEY POINTS: • DTI and tractography can evaluate renal allograft function at an early stage • Medullary FA, cortical and medullary ADC can effectively evaluate allograft function • Medullary FA, cortical and medullary ADC are correlated with eGFR in renal allografts • Medullary ADC increased and cortical FA decreased in stable allografts compared to control subjects • Medullary FA, cortical and medullary ADC decreased and allograft function declined.

[Longitudinal evaluation of reparative cartilage after matrix-associated autologous chondrocyte implantation with delayed gadolinium-enhanced MRI of the cartilage].

OBJECTIVE: To estimate zonal variation of GAG content in reparative cartilage after matrix associated autologous chondrocyte implantation (MACI) using delayed gadolinium-enhanced magnetic resonance imaging of the cartilage (dGEMRIC). METHODS: Seven patients (14 cartilage defects) undergoing MACI were recruited for examination with dGEMRIC at 3, 6, and 12 months after the procedure to calculate global and zonal longitudinal relaxivity (Δ R1) of the normal cartilage and reparative cartilage. RESULTS: The mean Δ R1 values of normal cartilage were significantly lower than those of reparative cartilage after MACI. A significant decrease was noted in the mean Δ R1 values from the deep layer to the superficial layer in the reparative cartilage at the 3 examinations. The Δ R1 values of the reparative cartilage showed no significant variation between 3 months and 6 months, but a significant decrease in the Δ R1 values occurred at 12 months. CONCLUSIONS: dGEMRIC is feasible to assess cartilage repair noninvasively following MACI.

[3T magnetic resonance T2 mapping for evaluation of cartilage repair after matrix-associated autologous chondrocyte transplantation].

OBJECTIVE: To assess the value of magnetic resonance imaging (MRI) T2 mapping in quantitative evaluation of cartilage repair following matrix-associated autologous chondrocyte transplantation (MACT). METHODS: Six patients (with 9 plug cartilages) following MACT underwent MRI on a 3.0 Tesla MR scan system at 3, 6 and 12 months after the surgery. The full-thickness and zonal areas (deep and superficial layers) T2 values were calculated for the repaired cartilage and control cartilage. RESULTS: The mean T2 values of the repaired cartilage after MACT were significantly higher than that of the control cartilages at 3 and 6 months (P<0.05), but not at 12 months (P=0.063). At 6 and 12 months, the T2 values of the superficial layers were significantly higher than those of the deep layers in the repaired cartilages (P<0.05). The zonal (deep and superficial layers) T2 values of the repaired cartilages decreased significantly over time at 6 and 12 months as compared to those at 3 months after the surgery (P<0.05). CONCLUSION: MRI T2 mapping can serve as an important modality for assessing the repair of the articular cartilage following MACT.

[Quantitative T2 mapping evaluates the repaired articular cartilage].

OBJECTIVE: To evaluate the value of T2 mapping in monitoring the repaired cartilage after matrix-associated autologous chondrocyte implantation/transplantation (MACI/MACT). METHODS: Four patients (10 plug cartilages) were examined three times by T2 mapping at 1, 3, and 6 months using a 3.0 Tesla MR scan system. Quantitative mean (full-thickness) T2 values were calculated in the transplanted area and control cartilage. Paired t-tests were used to compare the T2 values between transplanted and control cartilage. For analysis of longitudinal T2 values, one-way analyses of variance were performed among 1, 3, and 6 months after MACI. RESULTS: The mean T2 values of the transplanted area at 1, 3, and 6 months after MACI were (82.40±15.23), (71.09±13.06), (53.80±4.86) ms, respectively. There were significant differences between the transplanted and control cartilage at 1 and 3 months (both P<0.01) after MACI, but not at 6 months (P=0.196). There were significant differences among T2 values of 1, 3, and 6 months after MACI in transplanted area (P=0.03). CONCLUSION: T2 mapping provides a useful tool for monitoring the biochemical development of the transplanted cartilage and can be used to evaluate the cartilage repair noninvasively.

Impulse-dependent extracellular resting dopamine concentration in rat striatum in vivo.

The ambient resting dopamine (DA) concentration in brain regulates cognition and motivation. Despite its importance, resting DA level in vivo remains elusive. Here, by high-frequency stimulation of the medial forebrain bundle and immediately following the stimulus-induced DA overflow, we recorded a DA "undershoot" which is a temporal reduction of DA concentration to a level below the baseline. Based on the DA undershoot, we predicted a resting DA concentration of ∼73nM in rat striatum in vivo. Simulation studies suggested that removing basal DA by DAT during the post-stimulation inhibition of tonic DA release caused the DA undershoot, and the resting concentration of DA modulated the kinetics of the evoked DA transient. The DA undershoot was eliminated by either blocking D2 receptors with haloperidol or blocking the DA transporter (DAT) with cocaine. Therefore, the impulse-dependent resting DA concentration is in the tens of nanomolar range and is modulated by the presynaptic D2 receptors and the DAT in vivo.

Nicotine dynamically modulates dopamine clearance in rat striatum in vivo.

Nicotine binds to nicotinic acetylcholine receptors on dopaminergic terminals to evoke dopamine (DA) release. The clearance of released DA occurs rapidly through reuptake into nerve terminals through the DA transporter (DAT). However, whether nicotine modulates DAT function in vivo is still not well understood. In the present study, we determined the effect of nicotine on DA clearance using in vivo amperometric recording in the striatum of urethane-anesthetized rats. Stable DA release was evoked by electrical stimulation of the medial forebrain bundle (MFB). Subsequently, nicotine or saline was administered with MFB stimulation at 10-min intervals for 60 min. Kinetic analysis revealed that nicotine decreased the amplitude of DA overflow and the maximal DA clearance rate (V(max)) in response to stimulation of 96 pulses at 80 Hz. Surprisingly, nicotine enhanced the maximal DA clearance rate (V(max)) by stimulation of 768 pulses at 80 Hz. Furthermore, we found that this paradoxical effect of nicotine on V(max) depended on the stimulation pattern. These results suggest that nicotine may exert its addictive role by dynamically modulating DAT function in vivo.

Role of vesicle pools in action potential pattern-dependent dopamine overflow in rat striatum in vivo.

Action potential (AP) patterns and dopamine (DA) release are known to correlate with rewarding behaviors, but how codes of AP bursts translate into DA release in vivo remains elusive. Here, a given AP pattern was defined by four codes, termed total AP number, frequency, number of AP bursts, and interburst time [N, f, b, i].. The 'burst effect' was calculated by the ratio (γ) of DA overflow by multiple bursts to that of a single burst when total AP number was fixed. By stimulating the medial forebrain bundle using AP codes at either physiological (20 Hz) or supraphysiological (80 Hz) frequencies, we found that DA was released from two kinetically distinct vesicle pools, the fast-releasable pool (FRP) and prolonged-releasable pool (PRP), in striatal dopaminergic terminals in vivo. We examined the effects of vesicle pools on AP-pattern dependent DA overflow and found, with given 'burst codes' [b=8, i=0.5 s], a large total AP number [N = 768, f = 80 Hz] produced a facilitating burst-effect (γ[b8/b1] = 126 ± 3%), while a small total AP number [N=96, 80 Hz] triggered a depressing-burst-effect (γ[b8/b1] = 29 ± 4%). Furthermore, we found that the PRP (but not the FRP) predominantly contributed to the facilitating-burst-effect and the FRP played an important role in the depressing-burst effect. Thus, our results suggest that striatal DA release captures pre-synaptic AP pattern information through different releasable pools.

Action potential bursts enhance transmitter release at a giant central synapse.

Patterns of action potentials (APs), often in the form of bursts, are critical for coding and processing information in the brain. However, how AP bursts modulate secretion at synapses remains elusive. Here, using the calyx of Held synapse as a model we compared synaptic release evoked by AP patterns with a different number of bursts while the total number of APs and frequency were fixed. The ratio of total release produced by multiple bursts to that by a single burst was defined as 'burst-effect'.We found that four bursts of 25 stimuli at 100 Hz increased the totalcharge of EPSCs to 1.47 ± 0.04 times that by a single burst of 100 stimuli at the same frequency.Blocking AMPA receptor desensitization and saturation did not alter the burst-effect, indicating that it was mainly determined by presynaptic mechanisms. Simultaneous dual recordings of presynaptic membrane capacitance (Cm) and EPSCs revealed a similar burst-effect, being 1.58±0.13by Cm and 1.49±0.05 by EPSCs. Reducing presynapticCa2+ influx by lowering extracellular Ca2+concentration or buffering residual intracellular Ca2+ with EGTA inhibited the burst-effect. We further developed a computational model largely recapitulating the burst-effect and demonstrated that this effect is highly sensitive to dynamic change in availability of the releasable pool of synaptic vesicles during various patterns of activities. Taken together, we conclude that AP bursts modulate synaptic output mainly through intricate interaction between depletion and replenishment of the large releasable pool. This burst-effect differs from the somatic burst-effect previously described from adrenal chromaffin cells, which substantially depends on activity-induced accumulation of Ca2+ to facilitate release of a limited number of vesicles in the releasable pool. Hence, AP bursts may play an important role in dynamically regulating synaptic strength and fidelity during intense neuronal activity at central synapses.

DTNBP1, a schizophrenia susceptibility gene, affects kinetics of transmitter release.

Schizophrenia is one of the most debilitating neuropsychiatric disorders, affecting 0.5-1.0% of the population worldwide. Its pathology, attributed to defects in synaptic transmission, remains elusive. The dystrobrevin-binding protein 1 (DTNBP1) gene, which encodes a coiled-coil protein, dysbindin, is a major susceptibility gene for schizophrenia. Our previous results have demonstrated that the sandy (sdy) mouse harbors a spontaneously occurring deletion in the DTNBP1 gene and expresses no dysbindin protein (Li, W., Q. Zhang, N. Oiso, E.K. Novak, R. Gautam, E.P. O'Brien, C.L. Tinsley, D.J. Blake, R.A. Spritz, N.G. Copeland, et al. 2003. Nat. Genet. 35:84-89). Here, using amperometry, whole-cell patch clamping, and electron microscopy techniques, we discovered specific defects in neurosecretion and vesicular morphology in neuroendocrine cells and hippocampal synapses at the single vesicle level in sdy mice. These defects include larger vesicle size, slower quantal vesicle release, lower release probability, and smaller total population of the readily releasable vesicle pool. These findings suggest that dysbindin functions to regulate exocytosis and vesicle biogenesis in endocrine cells and neurons. Our work also suggests a possible mechanism in the pathogenesis of schizophrenia at the synaptic level.