Diffusion-weighted MRI in prostate cancer -- comparison between single-shot fast spin echo and echo planar imaging sequences

Diffusion-weighted (DW) MRI at 1.5 T was carried out in two groups of patients. MRI data were correlated with the biopsy and histopathology (where available). The performance of two sequences -- a single-shot FSE (14 patients) and a single-shot EPI (15 patients) -- was compared. Average ADC values from the normal peripheral zone (PZ), central gland (CG) and the tumour [prostate carcinoma (PCa)] were calculated from b values of 0 and 600. Tukey-Kramer test was used for statistical analysis. EPI produced higher values of ADC (10(-3) mm(2)/s) than FSE sequence: 1.992+/-0.208 vs. 1.573+/-0.270 in PZ (P<.001), 1.518+/-0.126 vs. 1.373+/-0.179 in CG and 1.214+/-0.254 vs. 0.993+/-0.158 in PCa (P<.01). In conclusion, both EPI and FSE sequences showed differences in ADC between normal PZ, CG and PCa; however, EPI produced significantly higher ADC values than FSE.     

Diffusion-weighted magnetic resonance imaging of human skeletal muscles: gender-, age- and muscle-related differences in apparent diffusion coefficient

Purpose

To evaluate the apparent diffusion coefficient (ADC) of skeletal muscle based on signal intensity (SI) attenuation vs. increasing b values and to determine ADC differences in skeletal muscles between genders, age groups and muscles.

Materials and Methods

Diffusion-weighted images (b values in the range of 0–750 s/mm² at increments of 50 s/mm²) of the ankle dorsiflexors (116 subjects) and the erector spinae muscles (86 subjects) were acquired with a 1.5-T MR device. From the two different slopes obtained in SI vs. b-value logarithmic plots, ADC^b0–50 (b values=0 and 50 s/mm²) reflected diffusion and perfusion, while ADC^b50–750 (b values in the range of 50–750 s/mm² at increments of 50 s/mm²) approximated the true diffusion coefficient. Moreover, to evaluate whether this b-value combination is appropriate for assessing the flow component within muscles, diffusion-weighted images of the ankle dorsiflexors (10 subjects) were obtained before and during temporal arterial occlusion.

Results

ADC^b0–50 and ADC^b50–750 were found to be 2.64×10^–3 and 1.44×10^–3 mm²/s in the ankle dorsiflexors, and 3.02×10^–3 and 1.49×10^–3 mm²/s in the erector spinae muscles, respectively. ADC^b0–50 was significantly higher than ADC^b50–750 in each muscle (P<.01). The erector spinae muscles showed significantly higher ADC values than the ankle dorsiflexors (P<.01). However, for each muscle, there were few significant gender- and age-related ADC differences. Following temporal occlusion, ADC^b0–50 of the ankle dorsiflexors decreased significantly from 2.49 to 1.6×10^–3 mm²/s (P<.01); however, ADC^b50–750 showed no significant change.

Conclusion

Based on the SI attenuation pattern, muscle ADC could be divided into ADC that reflects both diffusion and perfusion, and ADC that approximates a true diffusion coefficient. There were significant differences in ADC of functionally distinct muscles. However, we barely found any gender- or age-related ADC differences for each muscle.     

Abdominal apparent diffusion coefficient measurements: effect of diffusion-weighted image quality and usefulness of anisotropic images

This study aimed to assess the effect of diffusion-weighted image (DWI) quality on abdominal apparent diffusion coefficient (ADC) measurements and the usefulness of anisotropic images. Twenty-six patients (10 men and 16 women; mean, 58.1 years) who underwent DW imaging and were diagnosed not to have any abdominal diseases were analyzed. Single-shot spin-echo echo-planar DW imaging was performed, and one isotropic and three orthogonal anisotropic images were created. ADCs were calculated for liver (four segments), spleen, pancreas (head, body, tail) and renal parenchyma. Image quality for each organ part was scored visually. We estimated the correlation between ADC and image quality and evaluated the feasibility of using anisotropic images. ADCs and image quality were affected by motion probing gradient directions in the liver and pancreas. A significant inverse correlation was found between ADC and image quality. The r values for isotropic images were −.46, −.48, −.70 and −.28 for the liver, spleen, pancreas and renal parenchyma, respectively. Anisotropic images had the best quality and lowest ADC in at least one organ part in 17 patients. DWIs with the best quality among isotropic and anisotropic images should be used in the liver and pancreas.     

Role of apparent diffusion coefficient values for the differentiation of viable and necrotic areas of breast cancer and its potential utility to guide voxel positioning for MRS in the absence of dynamic contrast-enhanced MRI data

We carried out retrospective analysis of apparent diffusion coefficient (ADC) values in 48 infiltrating ductal breast cancer patients who had dynamic contrast-enhanced magnetic resonance imaging (DCEMRI; Group I) and in 53 patients (Group II) for whom DCEMRI data were not available. Twenty-three patients of Group I showed no necrosis (Group Ia), while in 25 patients, both viable (nonnecrotic) and necrotic tumor areas (Group Ib) were observed on DCEMRI. T1-weighted, fat-suppressed and short inversion recovery images were used to identify the viable and necrotic tumor areas in Group II patients, and necrosis was not seen in 11 patients (Group IIa), while 42 (Group IIb) showed both viable and necrotic tumor areas. The ADCs of the necrotic area of Group Ib (1.79±0.30 ×10(-3) mm(2)/s) and Group IIb (1.83±0.40 ×10(-3) mm(2)/s) patients were similar and significantly higher (P<.01) compared to the ADCs of the viable tumor area of Group Ia (0.96±0.21 ×10(-3) mm(2)/s) and Group IIa (0.90±0.17 ×10(-3) mm(2)/s) patients. Proton MR spectroscopy (MRS) data were also available in these patients, and the ADC values were retrospectively determined from the voxel from which MR spectrum was obtained. These values were compared with the ADC obtained for the viable and necrotic areas of the tumor. ADC of the MRS voxel was similar to that obtained for the viable tumor area in patients of both groups. This interesting observation reveals the potential utility of using ADC values to identify viable tumor area for positioning of voxel for MRS in the absence of DCEMRI data.     

Diffusion-weighted imaging in the prostate: an apparent diffusion coefficient comparison of half-Fourier acquisition single-shot turbo spin-echo and echo planar imaging

Prostate cancer detection using diffusion-weighted imaging is highly affected by the accuracy of the apparent diffusion coefficient (ADC) values in an image. Echo planar imaging (EPI) is a fast sequence commonly used for diffusion imaging but has inherent magnetic susceptibility and chemical shift artefacts associated. A diffusion sequence that is less affected by these artefacts is therefore advantageous. The half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence was chosen. The diffusion sequences were compared in image quality, repeatability of the ADC value and the effect on the ADC value with varied b values. Eight volunteers underwent three scans of each sequence, on a 1.5-T Siemens system, using b values of 0, 150, 300, 450, 600, 750, 900 and 1000 s/mm(2). ADC maps were created to address the reproducibility of the ADC value when using two b values compared to eight b values. The ADC value using all b values with the HASTE sequence gave the best performance in all tested categories. Both sequences gave significantly different ADC mean values for two b values compared to when using eight b values (P<.05) suggesting larger error is present when using two b values. HASTE was shown to be an improvement over EPI in terms of repeatability, signal variation within a region of interest and standard deviation over the volunteer set. The improved accuracy of the ADC value in the HASTE sequence makes it potentially a more sensitive tumor detection technique.     

High resolution diffusion weighted magnetic resonance imaging of the pancreas using reduced field of view single-shot echo-planar imaging at 3 T

Diffusion weighted magnetic resonance imaging (DWI) has been mostly acquired using single-shot echo-planar imaging (ss EPI) to minimize motion induced artifacts. The spatial resolution, however, is inherently limited in ss EPI especially for abdominal imaging, even with the advances in parallel imaging. A novel method of reduced Field of View ss EPI (rFOV ss EPI) has achieved high resolution DWI in human carotid artery, spinal cord with reduced blurring and higher spatial resolution than conventional ss EPI, but it has not been used to pancreas imaging. In the work, comparisons between the full FOV ss-DW EPI and rFOV ss-DW EPI in image qualities and ADC values of pancreatic tumors and normal pancreatic tissues were performed to demonstrate the feasibility of pancreatic high resolution rFOV DWI. There were no significant differences in the mean ADC values between full FOV DWI and rFOV DWI for the 17 subjects using b = 600 s/mm² (P = 0.962). However, subjective scores of image quality was significantly higher at rFOV ss DWI (P = 0.008 and 0.000 for b-value = 0 s/mm² and 600 s/mm² respectively). The spatial resolution of DWI for pancreas was increased by a factor of over 2.0 (from almost 3.0 mm/pixel to 1.25 mm/pixel) using rFOV ss EPI technique. Reduced FOV ss EPI can provide good DW images and is promising to benefit applications for pancreatic diseases.     

Diffusion-weighted imaging of local recurrent prostate cancer after radiation therapy: comparison with 22-core three-dimensional prostate mapping biopsy

Accurate localization of local recurrence within the prostate gland is important to perform focal salvage therapy effectively with minimal complications. The purpose of this study was to evaluate the usefulness of diffusion-weighted imaging (DWI) in the detection and localization of prostate cancer recurrence in patients with biochemical failure after definitive radiation therapy using 22-core three-dimensional prostate mapping biopsy (3D-PMB) as a standard reference. Ten patients who underwent magnetic resonance imaging and 22-core 3D-PMB were retrospectively analyzed. For visual assessment of DWI, the prostate was divided into 22 regions corresponding to 3D-PMB. Two diagnostic radiologists determined the presence of abnormal high signal intensity in each region on DWI, and the results of DWI were compared with those of 3D-PMB. Of the 220 regions, 16 regions in six patients were positive for cancer on 3D-PMB, and 30 regions in six patients were judged as positive on DWI. On a patient-by-patient basis, sensitivity and specificity were 100% (6/6) and 100% (4/4), respectively. On a region-by-region basis, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 69% (11/16), 91% (185/204), 37% (11/30), 97% (185/190) and 89% (196/220), respectively. For discrepant localization between DWI and pathology, DWI-positive and pathology-positive regions tended to be adjacent to each other. In conclusion, DWI is a useful tool for the detection and localization of recurrent prostate cancer in patients with biochemical failure after radiation therapy and may be helpful in the planning of focal salvage therapy.     

Diffusion-weighted MRI: influence of intravoxel fat signal and breast density on breast tumor conspicuity and apparent diffusion coefficient measurements

Promising recent investigations have shown that breast malignancies exhibit restricted diffusion on diffusion-weighted imaging (DWI) and may be distinguished from normal tissue and benign lesions in the breast based on differences in apparent diffusion coefficient (ADC) values. In this study, we assessed the influence of intravoxel fat signal on breast diffusion measures by comparing ADC values obtained using a diffusion-weighted single shot fast spin-echo sequence with and without fat suppression. The influence of breast density on ADC measures was also evaluated. ADC values were calculated for both tumor and normal fibroglandular tissue in a group of 21 women with diagnosed breast cancer. There were systematic underestimations of ADC for both tumor and normal breast tissue due to intravoxel contribution from fat signal on non–fat-suppressed DWI. This ADC underestimation was more pronounced for normal tissue values (mean difference=40%) than for tumors (mean difference=27%, P<.001) and was worse in women with low breast tissue density vs. those with extremely dense breasts (P<.05 for both tumor and normal tissue). Tumor conspicuity measured by contrast-to-noise ratio was significantly higher on ADC maps created with fat suppression and was not significantly associated with breast density. In summary, robust fat suppression is important for accurate breast ADC measures and optimal lesion conspicuity on DWI.     

Transfer characteristics of arterial pulsatile force in regional intracranial tissue using dynamic diffusion MRI: A phantom study

Introduction

To clarify the mechanism underlying apparent diffusion coefficient (ADC) changes in regional intracranial tissue during the cardiac cycle, we investigated relationships among ADC changes, volume loading, and intracranial pressure using a hemodialyzer phantom in magnetic resonance imaging (MRI).

Materials and Methods

The hemodialyzer phantom consisted of hollow fibers (HF), the external space of HFs (ES), and a gateway of dialysis solution, filled with syrup solution and air. The high-volume and low-volume loadings were periodically applied to HFs by a to-and-fro flow pump, and syrup solution was permitted to enter or leave HFs during the volume loading cycles. ADC maps at each volume loading phase were obtained using ECG-triggered single-shot diffusion echo-planar imaging. Dynamic phase contrast MRI was also used to measure volume loading to the phantom. We compared the ADC changes, volume loading, and intracranial pressure in the phantom during the cardiac cycle.

Results

ADC changes synchronized significantly with absolute volumetric flow rate change. The maximum ADC change was higher in high-volume loading cycles than in low-volume loading cycles. Results showed that the water molecules in ES fluctuated according to the force transferred from HF to ES. ADC changes were dependent upon the volumetric flow rate during the cardiac cycle.

Conclusions

Our original phantom allowed us to clarify the mechanism underlying water fluctuations in intracranial tissues. Measurement of maximum changes in ADC is an effective method to define the transfer characteristics of the arterial pulsatile force in regional intracranial tissue.     

Comparison of accuracy of intravoxel incoherent motion and apparent diffusion coefficient techniques for predicting malignancy of head and neck tumors using half-Fourier single-shot turbo spin-echo diffusion-weighted imaging

Purpose

To evaluate the use of the intravoxel incoherent motion (IVIM) technique in half-Fourier single-shot turbo spin-echo (HASTE) diffusion-weighted imaging (DWI), and to compare its accuracy to that of apparent diffusion coefficient (ADC) to predict malignancy in head and neck tumors.

Patients and methods

HASTE DW images of 33 patients with head and neck tumors (10 benign and 23 malignant) were evaluated. Using the IVIM technique, parameters (D, true diffusion coefficient; f, perfusion fraction; D*, pseudodiffusion coefficient) were calculated for each tumor. ADC values were measured over a range of b values from 0 to 1000 s/mm². IVIM parameters and ADC values in benign and malignant tumors were compared using Student's t test, receiver operating characteristics (ROC) analysis, and multivariate logistic regression modeling.

Results

Mean ADC and D values of malignant tumors were significantly lower than those of benign tumors (P < 0.05). Mean D* values of malignant tumors were significantly higher than those of benign tumors (P < 0.05). There was no significant difference in mean f values between malignant and benign tumors (P > 0.05). The technique of combining D and D* was the best for predicting malignancy; accuracy for this model was higher than that for ADC.

Conclusions

The IVIM technique may be applied in HASTE DWI as a diagnostic tool to predict malignancy in head and neck masses. The use of D and D* in combination increases the diagnostic accuracy in comparison with ADC.     

Biexponential analysis of diffusion-related signal decay in normal human cortical and deep gray matter

Diffusion imaging with high-b factors, high spatial resolution and cerebrospinal fluid signal suppression was performed in order to characterize the biexponential nature of the diffusion-related signal decay with b-factor in normal cortical gray and deep gray matter (GM). Integration of inversion pulses with a line scan diffusion imaging sequence resulted in 91% cerebrospinal fluid signal suppression, permitting accurate measurement of the fast diffusion coefficient in cortical GM (1.142+/-0.106 microm2/ms) and revealing a marked similarity with that found in frontal white matter (WM) (1.155+/-0.046 microm2/ms). The reversal of contrast between GM and WM at low vs high b-factors is shown to be due to a significantly faster slow diffusion coefficient in cortical GM (0.338+/-0.027 microm2/ms) than in frontal WM (0.125+/-0.014 microm2/ms). The same characteristic diffusion differences between GM and WM are observed in other brain tissue structures. The relative component size showed nonsignificant differences among all tissues investigated. Cellular architecture in GM and WM are fundamentally different and may explain the two- to threefold higher slow diffusion coefficient in GM.     

Diagnostic performance of apparent diffusion coefficient and quantitative kinetic parameters for predicting additional malignancy in patients with newly diagnosed breast cancer

Purpose

To evaluate the diagnostic performance of an apparent diffusion coefficient (ADC) and quantitative kinetic parameters in patients with newly diagnosed breast cancer.

Materials and Methods

We enrolled 169 lesions in 89 patients with breast cancer who underwent dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI). Comparisons between benign and malignant lesions were performed for lesion type (mass or nonmass-like enhancement), size (≥ 1 cm or < 1 cm), ADC, kinetic parameters and the presence of a US correlate.

Results

There were 63 benign and 106 malignant lesions. The mean size and initial peak enhancement of the benign lesions were significantly lower than those of malignant lesions (P < 0.001 for both). The ADC of the benign lesions was significantly higher than that of malignant lesions (1.42 × 10^− 3 mm²/sec vs. 1.04 × 10^− 3 mm²/sec; P < 0.001). The area under the receiver operating characteristic curve (AUC) for predicting malignancy was 0.87 for the combined parameters of size, ADC, and initial peak enhancement, which was higher than those of each parameter.

Conclusions

Combination of quantitative kinetic parameters and ADC showed higher diagnostic performance for predicting malignancy than each parameter alone for the evaluation of patients with breast cancer.     

Intravoxel incoherent motion imaging of the kidney: alterations in diffusion and perfusion in patients with renal dysfunction

Purpose

To investigate the relationship between estimated glomerular filtration rate (eGFR) and parameters calculated using intravoxel incoherent motion (IVIM) imaging of the kidneys.

Materials and Methods

We studied 365 patients, divided into 4 groups based on eGFR levels (mL/min/1.73 m²): group 1, eGFR ≥ 80(n = 80); group 2, eGFR 60–80 (n = 156); group 3, eGFR 30–60 (n = 114); and group 4 ,eGFR < 30 (n = 15). IVIM imaging was used to acquire diffusion-weighted images at 12 b values. The diffusion coefficient of pure molecular diffusion (D), the diffusion coefficient of microcirculation or perfusion (D*), and perfusion fraction (f) were compared among the groups using group 1 as control.

Results

In the renal cortex, D* values were significantly lower in groups 2, 3, and 4 than in group 1. The D value of renal cortex was significantly low in only group 3. In the renal medulla, the D* and D values were significantly lower only in groups 2 and 3, respectively.

Conclusion

As renal dysfunction progresses, renal perfusion might be reduced earlier and affected more than molecular diffusion in the renal cortex. These changes are effectively detected by IVIM MR imaging.     

Cardiac T2 measurements in patients with iron overload: a comparison of imaging parameters and analysis techniques

Measurement of cardiac T2 has emerged as an important tool to noninvasively quantify cardiac iron concentration in order to detect preclinical evidence of toxic levels and titrate chelation therapy. However, there exists variation among practitioners in cardiac T2 measurement methods. This study examines the impact of different imaging parameters and data analysis techniques on the calculated cardiac R2 (1/T2) in patients at risk for cardiac siderosis. The study group consisted of 36 patients with thalassemia syndromes who had undergone clinical magnetic resonance imaging assessment of cardiac siderosis using a standardized protocol and who were selected to yield a broad range of cardiac R2 values. Cardiac R2 measurements were performed on a 1.5-T scanner using an electrocardiogram-gated, segmented, multiecho gradient echo sequence obtained in a single breath-hold. R2 was calculated from the signal intensity versus echo time data in the ventricular septum on a single midventricular short-axis slice. There was good agreement between R2 measured with a blood suppression prepulse (black blood technique) and without (mean difference 6.0 ± 10.7 Hz). The black blood technique had superior within-study reproducibility (R2 mean difference 1.6 ± 8.6 Hz versus 2.7 ± 14.6 Hz) and better interobserver agreement (R2 mean difference 3.4 ± 8.2 Hz versus 8.3 ± 16.5 Hz). With the same minimum echo time, the use of small (1.0 ms) versus large (2.2 ms) echo spacing had minimal impact on cardiac R2 (mean difference 0.3 ± 8.7 Hz). The application of a region-of-interest-based versus a pixel-based data analysis also had little effect on cardiac R2 calculation (mean difference 8.4 ± 6.9 Hz). With black blood images, fitting the signal curve to a monoexponential decay or to a monoexponential decay with a constant offset yielded similar R2 values (mean difference 3.4 ± 8.1 Hz). In conclusion, the addition of a blood suppression prepulse for cardiac R2 measurement yields similar R2 values and improves reproducibility and interobserver agreement. The findings regarding other variations may be helpful in establishing a broadly accepted imaging and analysis technique for cardiac R2 calculation.     

Comparison of in vitro breast cancer visibility in analyser‐based computed tomography with histopathology,mammography, computed tomography and magnetic resonance imaging

High‐resolution analyser‐based X‐ray imaging computed tomography (HR ABI‐CT) findings on in vitro human breast cancer are compared with histopathology, mammography, computed tomography (CT) and magnetic resonance imaging. The HR ABI‐CT images provided significantly better low‐contrast visibility compared with the standard radiological images. Fine cancer structures indistinguishable and superimposed in mammograms were seen, and could be matched with the histopathological results. The mean glandular dose was less than 1 mGy in mammography and 12–13 mGy in CT and ABI‐CT. The excellent visibility of in vitro breast cancer suggests that HR ABI‐CT may have a valuable role in the future as an adjunct or even alternative to current breast diagnostics, when radiation dose is further decreased, and compact synchrotron radiation sources become available.     

Chemical exchange saturation transfer MR imaging of articular cartilage glycosaminoglycans at 3 T: Accuracy of B0 Field Inhomogeneity corrections with gradient echo method

Glycosaminoglycan Chemical Exchange Saturation Transfer (gagCEST) is an important molecular MRI methodology developed to assess changes in cartilage GAG concentrations. The correction for B₀ field inhomogeneity is technically crucial in gagCEST imaging. This study evaluates the accuracy of the B₀ estimation determined by the dual gradient echo method and the effect on gagCEST measurements. The results were compared with those from the commonly used z-spectrum method. Eleven knee patients and three healthy volunteers were scanned. Dual gradient echo B₀ maps with different ?TE values (1, 2, 4, 8, and 10 ms) were acquired. The asymmetry of the magnetization transfer ratio at 1 ppm offset referred to the bulk water frequency, MTR_asym(1 ppm), was used to quantify cartilage GAG levels. The B₀ shifts for all knee patients using the z-spectrum and dual gradient echo methods are strongly correlated for all ?TE values used (r = 0.997 to 0.786, corresponding to ?TE = 10 to 1 ms). The corrected MTR_asym(1 ppm) values using the z-spectrum method (1.34% ± 0.74%) highly agree only with those using the dual gradient echo methods with ?TE = 10 ms (1.72% ± 0.80%; r = 0.924) and 8 ms (1.50% ± 0.82%; r = 0.712). The dual gradient echo method with longer ?TE values (more than 8 ms) has an excellent correlation with the z-spectrum method for gagCEST imaging at 3 T.     

Neuroprotective effect of agmatine in rats with transient cerebral ischemia using MR imaging and histopathologic evaluation

Purpose

This study aimed to further investigate the effects of agmatine on brain edema in the rats with middle cerebral artery occlusion (MCAO) injury using magnetic resonance imaging (MRI) monitoring and biochemical and histopathologic evaluation.

Materials and methods

Following surgical induction of MCAO for 90 min, agmatine was injected 5 min after beginning of reperfusion and again once daily for the next 3 post-operative days. The events during ischemia and reperfusion were investigated by T2-weighted images (T2WI), serial diffusion-weighted images (DWI), calculated apparent diffusion coefficient (ADC) maps and contrast-enhanced T1-weighted images (CE-T1WI) during 3 h–72 h in a 1.5 T Siemens MAGNETON Avanto Scanner. Lesion volumes were analyzed in a blinded and randomized manner. Triphenyltetrazolium chloride (TTC), Nissl, and Evans Blue stainings were performed at the corresponding sections.

Results

Increased lesion volumes derived from T2WI, DWI, ADC, CE-T1WI, and TTC all were noted at 3 h and peaked at 24 h–48 h after MCAO injury. TTC-derived infarct volumes were not significantly different from the T2WI, DWI-, and CE-T1WI-derived lesion volumes at the last imaging time (72 h) point except for significantly smaller ADC lesions in the MCAO model (P < 0.05). Volumetric calculation based on TTC-derived infarct also correlated significantly stronger to volumetric calculation based on last imaging time point derived on T2WI, DWI or CE-T1WI than ADC (P < 0.05). At the last imaging time point, a significant increase in Evans Blue extravasation and a significant decrease in Nissl-positive cells numbers were noted in the vehicle-treated MCAO injured animals. The lesion volumes derived from T2WI, DWI, CE-T1WI, and Evans blue extravasation as well as the reduced numbers of Nissl-positive cells were all significantly attenuated in the agmatine-treated rats compared with the control ischemia rats (P < 0.05).

Conclusion

Our results suggest that agmatine has neuroprotective effects against brain edema on a reperfusion model after transient cerebral ischemia.