Acute stress impairs set-shifting but not reversal learning.

The ability to update and modify previously learned behavioral responses in a changing environment is essential for successful utilization of promising opportunities and for coping with adverse events. Valid models of cognitive flexibility that contribute to behavioral flexibility include set-shifting and reversal learning. One immediate effect of acute stress is the selective impairment of performance on higher-order cognitive control tasks mediated by the medial prefrontal cortex (mPFC) but not the hippocampus. Previous studies show that the mPFC is required for set-shifting but not for reversal learning, therefore the aim of the present experiment is to assess whether exposure to acute stress (15 min of mild tail-pinch stress) given immediately before testing on either a set-shifting or reversal learning tasks would impair performance selectively on the set-shifting task. An automated operant chamber-based task, confirmed that exposure to acute stress significantly disrupts set-shifting but has no effect on reversal learning. Rats exposed to an acute stressor require significantly more trials to reach criterion and make significantly more perseverative errors. Thus, these data reveal that an immediate effect of acute stress is to impair mPFC-dependent cognition selectively by disrupting the ability to inhibit the use of a previously relevant cognitive strategy.

Evaluation of endorectal and urethral cooling devices during MR-guided ultrasound thermal ablation in canine prostate.

High-temperature thermal therapy for the treatment of prostate cancer is currently being applied as a minimally-invasive alternative over traditional forms of treatment. Catheter-based interstitial and transurethral ultrasound applicators are being developed for controlled and selective thermal ablation of prostaric tissues with concurrent MR thermal imaging. As part of this treatment strategy we have devised a transurethral cooling catheter and a cooling jacket to be placed over the endorectal MR imaging coil to protect the urethral mucosa and rectal wall from thermal damage during treatment. The cooling efficiencies and protective abilities of these devices were evaluated in vivo within three canine prostate glands. Invasive and MR derived temperature measurements within the prostate and rectal wall indicate that the protective influence of the endorectal cooling extends 5-10 mm from the rectal wall into the dorsal prostate. The urethral cooling extends approximately 5 mm from the cooling balloon. The protective capabilities were further verified with subsequent histological analysis with TTC stained tissue sections and contrast enhanced T1-weighted MR images post treatment. Both of these cooling devices are compatible with the MR thermometry and can be used to protect the urethral mucosa and rectal wall during prostate thermal ablation with interstitial and transurethral ultrasound devices.

MRI-guided laser thermal ablation: model to predict cell death from MR thermometry images for real-time therapy monitoring.

Solid tumors and other pathologies can be treated using laser thermal ablation under interventional magnetic resonance imaging (iMRI) guidance. We developed a model to predict cell death from MR thermometry measurements and applied it to in vivo rabbit brain data. To align post-ablation T2-weighted spin-echo MR lesion images to gradient echo MR images, from which temperature is derived, we used a registration method that aligned fiducials placed near the thermal lesion. We used the outer boundary of the hyperintense rim in the post-ablation MR lesion image as the boundary for cell death, as verified from histology. Model parameters were simultaneously estimated using an iterative optimization algorithm applied to every interesting pixel in 328 images from multiple experiments having various temperature histories. For a necrotic region of 766 voxels across all lesions, the model gave a voxel specificity and sensitivity of 98.1% and 78.4%, respectively. Median distance between the segmented necrotic boundary and the mislabeled voxels was within one MR voxel. Furthermore, our model predicted fewer errors as compared to the critical temperature cell death model. This is good evidence that iMRI temperature maps can be used with our model to predict therapeutic regions in real-time.

Catheter-based ultrasound applicators for selective thermal ablation: progress towards MRI-guided applications in prostate.

High-temperature thermal therapy is emerging as a feasible treatment option for prostate cancer and benign prostatic hyperplasia. Previous investigations have demonstrated distinct advantages of catheter-based ultrasound technology over other heating modalities for thermal ablation therapies, with significant potential for better spatial control and faster heating times. The purpose of this study was to develop ultrasound devices and techniques specifically for treating prostate cancer in conjunction with magnetic resonance thermal imaging (MRTI) to monitor and control treatment progression. Directional transurethral applicators have been designed with arrays of sectored tubular (90 degrees active acoustic sector) or with narrow planar transducer segments and integrated with a flexible delivery catheter with a cooling balloon. This applicator can be rotated within the prostatic urethra to target specific regions during treatment. MRI compatible catheter-cooled interstitial ultrasound applicators with 180 degrees active acoustic sectors were developed specifically to treat the prostate. These applicators may be implanted through the perineum into the posterior portion of the prostate, with their heating energy directed away from the rectum. Both heating strategies were evaluated via biothermal simulations and in vivo experiments within canine prostate (n = 3). During the in vivo studies, MRTI was used to monitor treatment temperatures, cytotoxic thermal doses (t43 > 240 min) and corresponding maximum temperature thresholds (Tmax > 52 degrees C) within three imaging planes simultaneously. Urethral and endorectal cooling was employed with both treatment strategies to provide further protection of the urethral mucosa and rectum from thermal damage. Results using the transurethral applicators demonstrated that narrow zones of coagulation (approximately 30 degrees sector for planar, approximately 90 degrees for tubular), extending up to 20 mm from the urethra to the periphery of the prostate gland, could be produced within 10-15 min. Further, rotation of the applicator during treatment could be used to destroy larger regions in the prostate. Experiments using multiple interstitial directional applicators (approximately 180 degrees active sectors), implanted within the posterior margin of the prostate with the energy directed away from the rectum, produced contiguous zones of thermal coagulation which extended from the posterior prostate toward the anterior-lateral periphery of the gland. Both transurethral and interstitial treatment strategies demonstrated significant potential for thermal ablation of localized prostate cancer, particularly when MRTI is used to guide and assess treatment.

First use of a truly-hybrid X-ray/MR imaging system for guidance of brain biopsy.

The use of a new hybrid imaging system for guidance of a brain biopsy is described. The system combines the strengths of MRI (soft-tissue contrast, arbitrary plane selection) with those of x-ray fluoroscopy (high-resolution real-time projection images, clear portrayal of bony structures) and allows switching between the imaging modalities without moving the patient. The biopsy was carried out using x-ray guidance for direction of the needle through the foramen ovale and MR guidance to target the soft-tissue lesion. Appropriate samples were acquired. The system could be particularly effective for guidance of those cases where motion, swelling, resection and other intra-operative anatomical changes cannot be accounted for using traditional stereotactic-based imaging approaches.

Temperature mapping of frozen tissue using eddy current compensated half excitation RF pulses.

Cryosurgery has been shown to be an effective therapy for prostate cancer. Temperature monitoring throughout the cryosurgical iceball could dramatically improve efficacy, since end temperatures of at least -40 degrees C are required. The results of this study indicate that MR thermometry based on tissue R(*)(2) has the potential to provide this information. Frozen tissue appears as a complete signal void on conventional MRI. Ultrashort echo times (TEs), achievable with half pulse excitation and a short spiral readout, allow frozen tissue to be imaged and MR characteristics to be measured. However, half pulse excitation is highly sensitive to eddy current distortions of the slice-select gradient. In this work, the effects of eddy currents on the half pulse technique are characterized and methods to overcome these effects are developed. The methods include: 1) eddy current compensated slice-select gradients, and 2) a correction for the phase shift between the first and second half excitations at the center of the slice. The effectiveness of these methods is demonstrated in R(*)(2) maps calculated within the frozen region during cryoablation.

Freehand iMRI-guided large-gauge core needle biopsy: a new minimally invasive technique for diagnosis of enhancing breast lesions.

The lack of reliable methods for minimally invasive biopsy of suspicious enhancing breast lesions has hindered the utilization of contrast-enhanced magnetic resonance imaging (MRI) for the detection and diagnosis of breast cancer. In this study, a freehand method was developed for large-gauge core needle biopsy (LCNB) guided by intraprocedural MRI (iMRI). Twenty-seven lesions in nineteen patients were biopsied using iMRI-guided LCNB without significant complications. Diagnostic tissue was obtained in all cases. Nineteen of the 27 lesions were subsequently surgically excised. Histopathologic analysis confirmed that iMRI-guided LCNB correctly distinguished benign lesions from malignancy in 18 of the 19 lesions. The histology revealed by core biopsy was partially discrepant with surgical biopsy in 2 of the other 19 lesions. Freehand iMRI-guided LCNB of enhancing breast lesions is promising. Larger studies are needed to determine the smallest lesion that can be sampled reliably and to precisely measure the accuracy of iMRI-guided LCNB as a minimally invasive tool to diagnose suspicious lesions found by breast MRI. J. Magn. Reson. Imaging 2001;13:896-902.

MRI study of immediate cell viability in focused ultrasound lesions in the rabbit brain.

The purpose of this study was to evaluate cell viability in MR imaged focused ultrasound (FUS) lesions using cell-viability staining with triphenyl tetrazolium chloride (TTC) and both light and electron microscopy. Ten paired ultrasonic lesions were created in 5 rabbit brains in vivo with an ultrasound beam of 1.5 MHz electrical power input to the transducer of 50 W and exposure duration of 15 seconds. T2-weighted fast spin-echo (FSE) MRI was performed to detect the FUS lesions in the brain 4 hours after treatment, after which the animals were immediately euthanized. Lesion sizes were measured on TTC-stained specimens, histological sections stained with hematoxylin and eosin (H&E), and T2-weighted MR images. The differences between the lesion diameters measured with the three methods were within the range of 0.1--0.7 mm. The lesion sizes measured from MRI correlated well with those seen from H&E sections. The measurements from MRI slightly overestimated lesion sizes on TTC-stained wet tissues by approximately one MRI pixel (0.31 mm). Electron microscopy demonstrated nuclear and cytoplasmic ultrastructural damage within the grey-white, non-TTC-stained lesion zone, whereas the TTC-stained normal tissue showed preservation of neuronal ultrastructure. Therefore, MR-imaged lesions represent a cell-death zone in rabbit brain 4 hours after FUS ablation, with slight overestimation by approximately one MRI pixel. J. Magn. Reson. Imaging 2001;13:23-30.

Temperature quantitation and mapping of frozen tissue.

A method was developed for quantitating the temperature within frozen tissue with the magnetic resonance (MR) parameter R2*. The pulse sequence uses half-pulse excitation and a short spiral readout to achieve echo times as short as 0.2 msec. Fiber-optic temperature sensors were inserted into bovine liver tissue. The tissue was frozen at one end while being held warm at the other end. Once steady state was reached, the parameter R2* was measured. A linear dependence of R2* on temperature was demonstrated. R2* is independent of freeze number and of the orientation of the temperature gradient with respect to the main magnetic field. Feasibility in a canine prostate during cryosurgery is demonstrated. J. Magn. Reson. Imaging 2001;13:99-104.

A truly hybrid interventional MR/X-ray system: feasibility demonstration.

A system enabling both x-ray fluoroscopy and MRI in a single exam, without requiring patient repositioning, would be a powerful tool for image-guided interventions. We studied the technical issues related to acquisition of x-ray images inside an open MRI system (GE Signa SP). The system includes a flat-panel x-ray detector (GE Medical Systems) placed under the patient bed, a fixed-anode x-ray tube overhead with the anode-cathode axis aligned with the main magnetic field and a high-frequency x-ray generator (Lunar Corp.). New challenges investigated related to: 1) deflection and defocusing of the electron beam of the x-ray tube; 2) proper functioning of the flat panel; 3) effects on B0 field homogeneity; and 4) additional RF noise in the MR images. We have acquired high-quality x-ray and MR images without repositioning the object using our hybrid system, which demonstrates the feasibility of this new configuration. Further work is required to ensure that the highest possible image quality is achieved with both MR and x-ray modalities.

Changes in posterior disc bulging and intervertebral foraminal size associated with flexion-extension movement: a comparison between L4-5 and L5-S1 levels in normal subjects.

BACKGROUND CONTEXT: No previous study has used magnetic resonance imaging (MRI) to evaluate changes of posterior disc bulging and intervertebral foraminal size in the normal spine with flexion-extension movement, comparing L4-5 versus L5-S1 intervertebral levels. PURPOSE: To determine changes in posterior disc bulging and intervertebral foraminal size with flexion-extension movement, comparing L4-5 versus L5-S1 intervertebral levels. STUDY DESIGN: An in vivo study of magnetic resonance kinematics with spine flexion extension. METHODS: Spines of three volunteers with no history of low back pain were scanned in neutral, flexion, and extension positions in a vertically open MRI system. MRI was repeated after 6 hours of normal activity and an additional 4 hours of heavy activity with a weighted vest. Posterior bulging of the intervertebral disc and the size of intervertebral foramen were measured at the L4-5 and L5-S1 levels. RESULTS: With spine flexion, posterior bulging of the discs increased at L4-5 in eight of nine measurements (three different spine-loading states for each of three subjects) and L5-S1 discs in six of nine measurements. In most cases, posterior bulging decreased with extension. No significant difference was noted in the degree of disc bulge between levels. Foraminal size at L4-5 increased with flexion and decreased with extension, and the extent of these changes was greater at the L4-5 level than at L5-S1. CONCLUSIONS: This pilot study demonstrates two distinct behavior characteristics of the normal spine with flexion-extension movement.

Truly hybrid interventional MR/X-ray system: investigation of in vivo applications.

RATIONALE AND OBJECTIVES: The purpose of this study was to provide in vivo demonstrations of the functionality of a truly hybrid interventional x-ray/magnetic resonance (MR) system. MATERIALS AND METHODS: A digital flat-panel x-ray system (1,024(2) array of 200 microm pixels, 30 frames per second) was integrated into an interventional 0.5-T magnet. The hybrid system is capable of MR and x-ray imaging of the same field of view without patient movement. Two intravascular procedures were performed in a 22-kg porcine model: placement of a transjugular intrahepatic portosystemic shunt (TIPS) (x-ray-guided catheterization of the hepatic vein, MR fluoroscopy-guided portal puncture, and x-ray-guided stent placement) and mock chemoembolization (x-ray-guided subselective catheterization of a renal artery branch and MR evaluation of perfused volume). RESULTS: The resolution and frame rate of the x-ray fluoroscopy images were sufficient to visualize and place devices, including nitinol guidewires (0.016-0.035-inch diameter) and stents and a 2.3-F catheter. Fifth-order branches of the renal artery could be seen. The quality of both real-time (3.5 frames per second) and standard MR images was not affected by the x-ray system. During MR-guided TIPS placement, the trocar and the portal vein could be easily visualized, allowing successful puncture from hepatic to portal vein. CONCLUSION: Switching back and forth between x-ray and MR imaging modalities without requiring movement of the patient was demonstrated. The integrated nature of the system could be especially beneficial when x-ray and MR image guidance are used iteratively.

The use of view angle tilting to reduce distortions in magnetic resonance imaging of cryosurgery.

Susceptibility artifacts from magnetic resonance (MR)-compatible cryoprobes can distort MR images of iceballs. In this work, we investigate the ability of view angle tilting (VAT) to correct susceptibility induced distortions in MR images of cryosurgery. The efficacy of VAT was tested in an ex vivo bovine liver model of cryosurgery using MR-compatible cryoprobes. Artifacts on high bandwidth fast spin echo images of freezing obtained with and without VAT were compared with photographs of the actual iceball shape and size. In vivo imaging with VAT was demonstrated during percutaneous MR-guided cryosurgery of pig liver and brain. VAT was most successful in reducing probe and iceball distortions when the imaging plane was normal to the cryoprobe, and the cryoprobe was perpendicular to the main magnetic field of the scanner. VAT had the greatest benefit when used to correct MR images of freezing when the surface of the iceball was relatively near to the cryoprobe. For large iceballs, the artifact was small so the VAT correction was less important. We conclude that VAT significantly reduced distortions in the shape of the signal void corresponding to the extent of freezing visualized during MR-guided cryosurgery. This improved ability to visualize the exact location of the cryoprobe, as well as the precise shape of the iceball, particularly during initial freezing when the iceball is small, has potential to significantly improve the accuracy of MR-guided cryosurgery of small lesions, and the accuracy of MR-assisted temperature calculations that are based on precise imaging of the probe location, and boundary geometry of the iceball.

Pulse sequences for interventional magnetic resonance imaging.

Interventional magnetic resonance imaging (iMRI) is different from diagnostic magnetic resonance imaging (MRI) in its spatial, temporal, and contrast resolution requirements due to its specific clinical applications. As a result, the pulse sequences used in iMRI often are significantly different than those used in the more conventional diagnostic arena. The focus of this article is to summarize how iMRI is different from diagnostic MRI, to describe a variety of MRI pulse sequences and sequence strategies that have evolved because of these differences, and to describe some MRI sequence strategies that are in development and may be seen in future iMRI applications.

Glenohumeral relationships during physiologic shoulder motion and stress testing: initial experience with open MR imaging and active imaging-plane registration.

PURPOSE: To test the hypotheses that open dynamic magnetic resonance (MR) imaging can (a) be used to evaluate and define normal shoulder motion in active joint motion and muscle contraction and (b) be used in conjunction with physical examination. MATERIALS AND METHODS: With an open-configuration, 0.5-T MR imaging system and active image-plane tracking, 10 shoulders were studied in five asymptomatic subjects to establish normal patterns of glenohumeral motion during abduction and adduction and internal and external rotation. Preliminary studies of physical examination during MR imaging, in which a physician examiner applied mechanical force to the humeral head, were also performed. RESULTS: During abduction and adduction and internal and external rotation maneuvers with active subjects muscle contraction, the humeral head remained precisely centered on the glenoid fossa in all asymptomatic subjects, which is in agreement with findings of previous radiographic studies. Application of force to the humeral head by an examiner was associated with as much as 6 mm of anterior translation and 13 mm of posterior translation. CONCLUSION: Dynamic MR imaging of the glenohumeral joint is possible over a wide range of physiologic motion in vertically open systems. Use of an MR tracking coil enabled accurate tracking of the anatomy of interest. These preliminary measurements of normal glenohumeral motion patterns begin to establish normal ranges of motion and constitute a necessary first step in characterizing pathologic motion in patients with common clinical problems such as instability and impingement.

Study of focused ultrasound tissue damage using MRI and histology.

This paper reports on an experimental study of in vivo tissue damage in the rabbit brain with focused ultrasound (FUS) using magnetic resonance imaging (MRI) and histopathological analysis. Ten ultrasonic lesions (tissue damage) were created in five rabbits using a focused ultrasound beam of 1.5 MHz, electrical power input to the transducer of 70-85 W, and an exposure duration of 15-20 seconds. T1- and T2-weighted fast spin-echo (FSE) and Fluid attenuated inversion recovery (FLAIR) sequences were used to detect the ultrasonic lesions after treatment. Imaging was performed for 4-8 hours after treatment, after which the animals were immediately sacrificed. Ultrasonic lesion diameter was measured on MRI and histological sections after correction for tissue shrinkage during the histological processing. The T1-weighted images showed lesions poorly, whereas both T2-weighted and FLAIR images showed lesions clearly. The lesion diameters on both T2 and FLAIR imaging correlated well with measurements from histology. The time delay before lesions appeared on T2-weighted imaging was 15 minutes to 1 hour, depending on the exposure location in the brain. J. Magn. Reson. Imaging 1999;10:146-153.

Joint motion in an open MR unit using MR tracking.

A system for active scan plane guidance during kinematic magnetic resonance (MR) examination of joint motion was developed utilizing an external tracking coil and MR tracking software. In a phantom study and during upright, weight-bearing, physiologic knee flexion, the external tracking coil maintained the scan plane through desired structures. Thus, MR tracking provides a robust method to guide the scan plane during MR imaging of active joint motion.

1999 Gary J. Becker Young Investigator Award. MR-guided transjugular portosystemic shunt placement in a swine model.

PURPOSE: To evaluate the performance of portal venous puncture with use of magnetic resonance (MR) guidance, and to place a transjugular intrahepatic portosystemic shunt (TIPS) in a swine model. MATERIALS AND METHODS: A study of 12 swine was performed to evaluate the ability of interventional MR imaging to guide portal vein puncture and TIPS placement. Six swine had catheters placed in the right hepatic vein under C-arm fluoroscopy. A nitinol guide wire was left in the vein and the animals were then moved into an open configuration MR imaging unit. A TIPS needle set was used to puncture the portal vein using MR fluoroscopy. The animals were transferred to the C-arm, and venography confirmed portal vein puncture. A follow-up study was performed in six additional swine to place a TIPS using only MR imaging guidance. MR tracking was used to advance a catheter from the right atrium into the inferior vena cava. Puncture of the portal vein was performed and a nitinol stent was placed, bridging the hepatic parenchyma. MR venogram confirmed placement. RESULTS: Successful portal vein puncture was achieved in all animals. The number of punctures required decreased from 12 in the first animal to a single puncture in the last eight swine. A stent was successfully placed across the hepatic tract in all six swine. CONCLUSIONS: Real-time MR imaging proved to be a feasible method to guide portal vein puncture and TIPS placement in pigs.

Management of biopsy needle artifacts: techniques for RF-refocused MRI.

Several methods were investigated to improve the depiction of biopsy needles in radiofrequency (RF)-refocused magnetic resonance imaging. Distortion correction is performed by the use of view angle tilting (VAT): a gradient is employed on the slice-select axis during readout. Needle conspicuity is increased by offsetting the gradient echo from the spin echo and by inverting the 90 degrees RF pulse slice-select gradient. VAT effectively re-registers in-plane shifts. Since this method changes the projection angle through the slice, some structures appear blurred, while other structures appear sharper. VAT does not correct errors in slice selection. Offsetting the spin echo from the gradient echo increases needle conspicuity but can result in a shift in the apparent location of the needle. Inverting the 90 degrees slice-select gradient effectively increases the needle conspicuity with no shift in the needle location. These methods provide an easy and interactive means to manipulate needle artifacts but should be used cautiously.

Magnetic resonance imaging of frozen tissues: temperature-dependent MR signal characteristics and relevance for MR monitoring of cryosurgery.

Previously, the magnetic resonance (MR) imaging appearance of frozen tissues created during cryosurgery has been described as a signal void. In this work, very short echo times (1.2 msec) allowed MR signals from frozen tissues to be measured at temperatures down to -35 degrees C. Ex vivo bovine liver, muscle, adipose tissue, and water were imaged at steady-state temperatures from -78 degrees to +6 degrees C. Signal intensity, T2*, and T1 were measured using gradient-echo imaging. Signal intensity and T2* decrease monotonically with temperature. In the future, these MR parameters may be useful for mapping temperatures during cryosurgery.