Development of an MR-Guided Focused Ultrasound (MRgFUS) Lesioning Approach for the Fornix in the Rat Brain.

OBJECTIVE: High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive therapy to lesion brain tissue, used clinically in patients and pre-clinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement. METHODS: The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n = 7 lesions) was compared to a craniectomy approach (n = 22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using histologic methods from a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging. RESULTS: Comparing a motorized adjustment system (∼1 mm precision, n = 17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n = 14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. CONCLUSIONS: The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.

MR-Guided Focused Ultrasound Thalamotomy in the Setting of Aneurysm Clip.

We report on a 75-year-old woman with a history of right MCA aneurysm clipping and medically refractive right-hand tremor. We successfully performed focused ultrasound thalamotomy of the left ventral intermediate nucleus under MR imaging-guidance at 3T. A thorough pretreatment evaluation of MR thermometry was critical to ensure that adequate precision could be achieved at the intended target. The tremor showed a 75% decrease at 24 hours postprocedure and a 50% decrease at a 3-month follow-up. There were no immediate adverse events.

Validation of single reference variable flip angle (SR-VFA) dynamic T1 mapping with T2 * correction using a novel rotating phantom.

PURPOSE: To validate single reference variable flip angle (SR-VFA) dynamic T1 mapping with and without T2 * correction against inversion recovery (IR) T1 measurements. METHODS: A custom cylindrical phantom with three concentric compartments was filled with variably doped agar to produce a smooth spatial gradient of the T1 relaxation rate as a function of angle across each compartment. IR T1 , VFA T1 , and B1 + measurements were made on the phantom before rotation, and multi-echo stack-of-radial dynamic images were acquired during rotation via an MRI-compatible motor. B1 + -corrected SR-VFA and SR-VFA-T2 * T1 maps were computed from the sliding window reconstructed images and compared against rotationally registered IR and VFA T1 maps to determine the percentage error. RESULTS: Both VFA and SR-VFA-T2 * T1 maps fell within 10% of IR T1 measurements for a low rotational speed, with a mean accuracy of 2.3% ± 2.6% and 2.8% ± 2.6%, respectively. Increasing rotational speed was found to decrease the accuracy due to increasing temporal smoothing over ranges where the T1 change had a nonconstant slope. SR-VFA T1 mapping was found to have similar accuracy as the SR-VFA-T2 * and VFA methods at low TEs (˜<2 ms), whereas accuracy degraded strongly with later TEs. T2 * correction of the SR-VFA T1 maps was found to consistently improve accuracy and precision, especially at later TEs. CONCLUSION: SR-VFA-T2 * dynamic T1 mapping was found to be accurate against reference IR T1 measurements within 10% in an agar phantom. Further validation is needed in mixed fat-water phantoms and in vivo.

The influence of bone model geometries on the determination of skull acoustic properties.

In this study, we investigated the impact of various simulated skull bone geometries on the determination of skull speed of sound and acoustic attenuation values via optimization using transmitted pressure amplitudes beyond the bone. Using the hybrid angular spectrum method (HAS), we simulated ultrasound transmission through four model sets of different geometries involving sandwiched layers of diploë and cortical bone in addition to three models generated from CT images of ex-vivo human skull-bones. We characterized cost-function solution spaces for each model and, using optimization, found that when a model possessed appreciable variations in resolvable layer thickness, the predefined attenuation coefficients could be found with low error (RMSE < 0.01 Np/cm). However, we identified a spatial frequency cutoff in the models' geometry beyond which the accuracy of the property determination begins to fail, depending on the frequency of the ultrasound source. There was a large increase in error of the attenuation coefficients determined by the optimization when the variations in layer thickness were above the identified spatial frequency cutoffs, or when the lateral variations across the model were relatively low in amplitude. For our limited sample of three CT-image derived bone models, the attenuation coefficients were determined successfully. The speed of sound values were determined with low error for all models (including the CT-image derived models) that were tested (RMSE < 0.4 m/s). These results illustrate that it is possible to determine the acoustic properties of two-component models when the internal bone structure is taken into account and the structure satisfies the spatial frequency constraints discussed.

Evaluation of methemoglobin as an intravascular contrast agent: T1 relaxation time effect in a rabbit model.

OBJECTIVE: Alternative contrast agents for MRI are needed for individuals who may respond adversely to gadolinium, and need an intravascular agent for specific indications. One potential contrast agent is intracellular methemoglobin, a paramagnetic molecule that is normally present in small amounts in red blood cells. An animal model was used to determine whether methemoglobin modulation with intravenous sodium nitrite transiently changes the T1 relaxation of blood. METHODS: Four adult New Zealand white rabbits were treated with 30 mg intravenous sodium nitrite. 3D TOF and 3D MPRAGE images were acquired before (baseline) and after methemoglobin modulation. T1 of blood was measured with 2D ss EPl acquisitions with inversion recovery preparation performed at two-minute intervals up to 30 min. T1 maps were calculated by fitting the signal recovery curve within major blood vessels. RESULTS: Baseline T1 was 1758 ± 53 ms in carotid arteries and 1716 ± 41 ms in jugular veins. Sodium nitrite significantly changed intravascular T1 relaxation. The mean minimum value of T1 was 1126 ± 28 ms in carotid arteries 8 to 10 min after the injection of sodium nitrite. The mean minimum value of T1 was 1171 ± 52 ms in jugular veins 10 to 14 min after the injection of sodium nitrite. Arterial and venous T1 recovered to baseline after a period of 30 min. CONCLUSION: Methemoglobin modulation produces intravascular contrast on T1-weighted MRI in vivo. Additional studies are needed to safely optimize methemoglobin modulation and sequence parameters for maximal tissue contrast.

Influence of cerebrospinal fluid on power absorption during transcranial magnetic resonance-guided focused ultrasound treatment.

BACKGROUND: Ultrasound beam aberration correction is vital when focusing ultrasound through the skull bone in transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) applications. Current methods make transducer element phase adjustments to compensate for the variation in skull properties (shape, thickness, and acoustic properties), but do not account for variations in the internal brain anatomy. PURPOSE: Our objective is to investigate the effect of cerebrospinal fluid (CSF) and brain anatomy on beam focusing in tcMRgFUS treatments. METHODS: Simulations were conducted with imaging data from 20 patients previously treated with focused ultrasound for disabling tremor. The Hybrid Angular Spectrum (HAS) method was used to test the effect of including cerebral spinal fluid (CSF) and brain anatomy in determining the element phases used for aberration correction and beam focusing. Computer tomography (CT) and magnetic resonance imaging (MRI) images from patient treatments were used to construct a segmented model of each patient's head. The segmented model for treatment simulation consisted of water, skin, fat, brain, CSF, diploë, and cortical bone. Transducer element phases used for treatment simulation were determined using time reversal from the desired focus, generating a set of phases assuming a homogeneous brain in the intracranial volume, and a second set of phases assigning CSF acoustic properties to regions of CSF. In addition, for three patients, the relative effect of separately including CSF speed of sound values compared to CSF attenuation values was found. RESULTS: We found that including CSF acoustic properties (speed of sound and attenuation) during phase planning compared to phase correction without considering CSF increased the absorbed ultrasound power density ratios at the focus over a range of 1.06 to 1.29 (mean of 17% ± 6%) for 20 patients. Separately considering the CSF speed of sound and CSF attenuation showed that the increase was due almost entirely to including the CSF speed of sound; considering only the CSF attenuation had a negligible effect. CONCLUSIONS: Based on HAS simulations, treatment planning phase determination using morphologically realistic CSF and brain anatomy yielded an increase of up to 29% in the ultrasound focal absorbed power density. Future work will be required to validate the CSF simulations.

Simultaneous proton resonance frequency T1 - MR shear wave elastography for MR-guided focused ultrasound multiparametric treatment monitoring.

PURPOSE: To develop an efficient MRI pulse sequence to simultaneously measure multiple parameters that have been shown to correlate with tissue nonviability following thermal therapies. METHODS: A 3D segmented EPI pulse sequence was used to simultaneously measure proton resonance frequency shift (PRFS) MR thermometry (MRT), T1 relaxation time, and shear wave velocity induced by focused ultrasound (FUS) push pulses. Experiments were performed in tissue mimicking gelatin phantoms and ex vivo bovine liver. Using a carefully designed FUS triggering scheme, a heating duty cycle of approximately 65% was achieved by interleaving FUS ablation pulses with FUS push pulses to induce shear waves in the tissue. RESULTS: In phantom studies, temperature increases measured with PRFS MRT and increases in T1 correlated with decreased shear wave velocity, consistent with material softening with increasing temperature. During ablation in ex vivo liver, temperature increase measured with PRFS MRT initially correlated with increasing T1 and decreasing shear wave velocity, and after tissue coagulation with decreasing T1 and increasing shear wave velocity. This is consistent with a previously described hysteresis in T1 versus PRFS curves and increased tissue stiffness with tissue coagulation. CONCLUSION: An efficient approach for simultaneous and dynamic measurements of PRSF, T1 , and shear wave velocity during treatment is presented. This approach holds promise for providing co-registered dynamic measures of multiple parameters, which correlates to tissue nonviability during and following thermal therapies, such as FUS.

Validation of a drift-corrected 3D MR temperature imaging sequence for breast MR-guided focused ultrasound treatments.

Real-time temperature monitoring is critical to the success of thermally ablative therapies. This work validates a 3D thermometry sequence with k-space field drift correction designed for use in magnetic resonance-guided focused ultrasound treatments for breast cancer. Fiberoptic probes were embedded in tissue-mimicking phantoms, and temperature change measurements from the probes were compared with the magnetic resonance temperature imaging measurements following heating with focused ultrasound. Precision and accuracy of measurements were also evaluated in free-breathing healthy volunteers (N = 3) under a non-heating condition. MR temperature measurements agreed closely with those of fiberoptic probes, with a 95% confidence interval of measurement difference from -2.0 °C to 1.4 °C. Field drift-corrected measurements in vivo had a precision of 1.1 ± 0.7 °C and were accurate within 1.3 ± 0.9 °C across the three volunteers. The field drift correction method improved precision and accuracy by an average of 46 and 42%, respectively, when compared to the uncorrected data. This temperature imaging sequence can provide accurate measurements of temperature change in aqueous tissues in the breast and support the use of this sequence in clinical investigations of focused ultrasound treatments for breast cancer.

Association between high-risk extracranial carotid plaque and covert brain infarctions and cerebral microbleeds.

PURPOSE: Covert brain infarctions (CBIs) and cerebral microbleeds (CMBs) represent subclinical sequelae of ischemic and hemorrhagic cerebral small vessel disease, respectively. In addition to thromboembolic stroke, carotid atherosclerosis has been associated with downstream vascular brain injury, including inflammation and small vessel disease. The specific plaque features responsible for this are unknown. We aimed to determine the association of specific vulnerable carotid plaque features to CBIs and CMBs to better understand the relation of large and small vessel disease in a single-center retrospective observational study. METHODS: Intraplaque hemorrhage (IPH) and plaque ulceration were recorded on carotid MRA and total, cortical, and lacunar CBIs and CMBs were recorded on brain MR in 349 patients (698 carotid arteries). Multivariable Poisson regression was performed to relate plaque features to CBIs and CMBs. Within-subject analysis in those with unilateral IPH and ulceration was performed with Poisson regression. RESULTS: Both IPH and plaque ulceration were associated with total CBI (prevalence ratios (PR) 3.33, 95% CI: 2.16-5.15 and 1.91, 95% CI: 1.21-3.00, respectively), after adjusting for stenosis, demographic, and vascular risk factors. In subjects with unilateral IPH, PR was 2.83, 95% CI: 1.76-4.55, for CBI in the ipsilateral hemisphere after adjusting for stenosis. Among those with unilateral ulceration, PR was 1.82, 95% CI: 1.18-2.81, for total CBI ipsilateral to ulceration after adjusting for stenosis. No statistically significant association was seen with CMBs. CONCLUSION: Both IPH and plaque ulceration are associated with total, cortical, and lacunar type CBIs but not CMBs suggesting that advanced atherosclerosis contributes predominantly to ischemic markers of subclinical vascular injury.

Correction of heat-induced susceptibility changes in respiratory-triggered 2D-PRF-based thermometry for monitoring of magnetic resonance-guided hepatic microwave ablation in a human-like in vivo porcine model.

PURPOSE: To develop and evaluate susceptibility corrected 2D proton resonance frequency (PRF)-based magnetic resonance (MR)-thermometry for the accurate assessment of the ablation zone of hepatic microwave ablation (MWA). METHODS AND MATERIALS: Twelve hepatic MWA were performed in five LEWE minipigs with human-like fissure-free liver. Temperature maps during ablation of PRF-based MR-thermometry were corrected by modeling heat induced susceptibility changes. Ablation zones were determined using cumulative equivalent minutes at 43 °C (CEM43) as tissue damage model. T1 weighted (w) post-ablation contrast-enhanced (CE) MR-imaging and manually segmented postmortem histology were used for validation. The agreement of uncorrected (raw) and susceptibility corrected (corr) MR-thermometry with T1w post-ablation CE MR-imaging and histology was evaluated. The Wilcoxon-signed rank test and Bland-Altman analysis were applied. RESULTS: With the susceptibility corrected MR-thermometry a significantly increased dice coefficient (raw: 77% vs. corr: 83%, p < 0.01) and sensitivity (raw: 72% vs. corr: 82%, p < 0.01) was found for the comparison to T1w-CE imaging as well as histopathology (dice coefficients: raw: 76% vs. corr: 79%, p < 0.001; sensitivity: raw: 72% vs. corr: 74%, p < 0.001). While major axis length was significantly increased (7.1 mm, p < 0.001) and minor axis length significantly decreased (2.2 mm, p < 0.001) in uncorrected MR-thermometry compared to T1w-CE MR-imaging, no significant bias was found after susceptibility correction. CONCLUSION: Using susceptibility corrected 2D PRF-based MR-thermometry to predict the ablation zones of hepatic MWA provided a good agreement in comparison to T1w post-ablation CE MR-imaging and histopathology.

A k-space-based method to measure and correct for temporal B0 field variations in MR temperature imaging.

PURPOSE: Present a method to use change in phase in repeated Cartesian k-space measurements to monitor the change in magnetic field for dynamic MR temperature imaging. METHODS: The method is applied to focused ultrasound heating experiments in a gelatin phantom and an ex vivo salt pork sample, without and with simulated respiratory motion. RESULTS: In each experiment, phase variations due to B0 field drift and respiration were readily apparent in the measured phase difference. With correction, the SD of the temperature over time was reduced from 0.18°C to 0.14°C (no breathing) and from 0.81°C to 0.22°C (with breathing) for the gelatin phantom, and from 0.68°C to 0.13°C (no breathing) and from 1.06°C to 0.17°C (with breathing) for the pork sample. The accuracy in nonheated regions, assessed as the RMS error deviation from 0°C, improved from 1.70°C to 1.11°C (no breathing) and from 4.73°C to 1.47°C (with breathing) for the gelatin phantom, and from 5.95°C to 0.88°C (no breathing) and from 13.40°C to 1.73°C (with breathing) for the pork sample. The correction did not affect the temperature measurement accuracy in the heated regions. CONCLUSION: This work demonstrates that phase changes resulting from variations in B0 due to drift and respiration, commonly seen in MR thermometry applications, can be measured directly from 3D Cartesian acquisition methods. The correction of temporal field variations using the presented technique improved temperature accuracy, reduced variability in nonheated regions, and did not reduce accuracy in heated regions.

Effects of T2 * on accuracy and precision of dynamic T1 measurements using the single reference variable flip angle method: a simulation study.

PURPOSE: To study in simulation and in theory the accuracy and precision of dynamic T1 measurements obtained using the previously published single-reference variable flip angle (SR-VFA) technique, with a focus on the effects of dynamic changes in T2 * on the calculation. METHODS: Monte Carlo simulations were performed over 1000 noisy iterations for the VFA method, the SR-VFA method, and a proposed method, SR-VFA with a T2 * correction (SR-VFA-T2 *). Dynamic T1 estimates were calculated analytically for each method, with signals modeled by the steady-state spoiled gradient echo equation. The mean and standard deviation of these estimates were calculated and compared to truth, while varying repetition time (TR), baseline and dynamic T1 , echo time (TE), baseline and dynamic T2 *, flip angles, and the number of averages on baseline scans. Additionally, the variance of T1 in the SR-VFA and SR-VFA-T2 * methods was derived analytically based on the theory of propagation of errors. This equation was used to produce an inverse-variance weighted linear combination to improve T1 mapping precision in the SR-VFA-T2 * method. Flip angle sensitivity of dynamic T1 precision in the SR-VFA and SR-VFA-T2 * methods was also performed. RESULTS: Substantial bias can be produced by the SR-VFA method when the ratio of the T2 * decay of the dynamic signal versus that of the baseline signals deviates from 1, with a 0.01 deviation leading to approximately a 1% bias in cases of high SNR and TR ≫ T1 . This bias can be corrected by estimating the baseline and dynamic T2 * values in this ratio via multiecho measurements. The bias and precision of the SR-VFA-T2 * method, when normalized to scan time, is found to rival and sometimes improve upon the two flip angle VFA method when an inverse variance weighted linear combination is applied across its multiecho T1 maps. The analytic variance equation presented is found to be accurate within 1% relative to the Monte Carlo simulations over a broad parameter space. Flip angle ranges that maximize SR-VFA and SR-VFA-T2 *T1 precision over a broad parameter space are given, and each is defined relative to TR and T1 . CONCLUSIONS: Multiecho SR-VFA-T2 * T1 mapping is found in simulation and theory to be a promising alternative to the VFA method that maintains speed of the SR-VFA method with accuracy and precision similar to the VFA method.

MRI-compatible electromagnetic servomotor for image-guided medical robotics.

The soft-tissue imaging capabilities of magnetic resonance imaging (MRI) combined with high precision robotics has the potential to improve the precision and safety of a wide range of image-guided medical procedures. However, functional MRI-compatible robotics have not yet been realized in part because conventional electromagnetic servomotors can become dangerous projectiles near the strong magnetic field of an MRI scanner. Here we report an electromagnetic servomotor constructed from non-magnetic components, where high-torque and controlled rotary actuation is produced via interaction between electrical current in the servomotor armature and the magnetic field generated by the superconducting magnet of the MRI scanner itself. Using this servomotor design, we then build and test an MRI-compatible robot which can achieve the linear forces required to insert a large-diameter biopsy instrument in tissue during simultaneous MRI. Our electromagnetic servomotor can be safely operated (while imaging) in the patient area of a 3 Tesla clinical MRI scanner.

Quasistatic Solutions versus Full-Wave Solutions of Single-Channel Circular RF Receive Coils on Phantoms of Varying Conductivities at 3 Tesla.

PURPOSE: Although full-wave simulations could be used to aid in RF coil design, the algorithms may be too slow for an iterative optimization algorithm. If quasistatic simulations are accurate within the design tolerance, then their use could reduce simulation time by orders of magnitude compared to full-wave simulations. This paper examines the accuracy of quasistatic and full-wave simulations at 3 Tesla. METHODS: Three sets of eight coils ranging from 3-10 cm (24 total) were used to measure SNR on three phantoms with conductivities of 0.3, 0.6, and 0.9 S/m. The phantom conductivities were chosen to represent those typically found in human tissues. The range of coil element sizes represents the sizes of coil elements seen in typical coil designs. SNR was determined using the magnetic and electric fields calculated by quasistatic and full-wave simulations. Each simulated SNR dataset was scaled to minimize the root mean squared error (RMSE) when compared against measured SNR data. In addition, the noise values calculated by each simulation were compared against benchtop measured noise values. RESULTS: The RMSE was 0.285 and 0.087 for the quasistatic and full-wave simulations, respectively. The maximum and minimum quotient values, when taking the ratio of simulated to measured SNR values, were 1.69 and 0.20 for the quasistatic simulations and 1.29 and 0.75 for the full-wave simulations, respectively. The ratio ranges, for the calculated quasistatic and full-wave total noise values compared to benchtop measured noise values, were 0.83-1.06 and 0.27-3.02, respectively. CONCLUSIONS: Full-wave simulations were on average 3x more accurate than the quasistatic simulations. Full-wave simulations were more accurate in characterizing the wave effects within the sample, though they were not able to fully account for the skin effect when calculating coil noise.

Carotid Compliance and Parahippocampal and Hippocampal Volume over a 20-Year Period.

INTRODUCTION: We evaluated the association between carotid compliance, a measure of arterial stiffness, to parahippocampal volume (PHV) and hippocampal volume (HV) over 20 years later in the Atherosclerosis Risk in the Community study. METHODS: We included participants with common carotid compliance measurements at visit 1 (1987-1989) and volumetric brain MRI at visit 5 (2011-2013). The primary outcomes are pooled bilateral PHV and HV. We performed linear regression models adjusting for age, sex, vascular risk factors, and total brain volume. RESULTS: Of the 614 participants, higher compliance was correlated with higher PHV (R = 0.218[0.144-0.291], p < 0.001) and HV (R = 0.181 [0.105-0.255, p < 0.001]). The association was linear and significant after adjusting for confounders. At follow-up MRI, 30 patients with dementia had lower PHV and HV than patients without dementia (p < 0.001 and p < 0.001, respectively). CONCLUSION: Carotid compliance is associated with higher PHV and HV when measured 20 years later, further supporting the link between arterial stiffness and cognitive decline.

A T1-based correction method for proton resonance frequency shift thermometry in breast tissue.

PURPOSE: Develop and evaluate the effectiveness of a T1-based correction method for errors in proton resonant frequency shift thermometry due to non-local field effects caused by heating in fatty breast tissues. METHODS: Computational models of human breast tissue were created by segmenting MRI data from a healthy human volunteer. MR-guided focused ultrasound (MRgFUS) heating and MR thermometry measurements were simulated in several locations in the heterogeneous segmented breast models. A T1-based correction method for PRF thermometry errors was applied and the maximum positive and negative errors and the root mean squared error (RMSE) in a region around each heating location was evaluated with and without correction. The method uses T1 measurements to estimate the temperature change in fatty tissues and correct for their influence. Experimental data from a heating study in cadaver breast tissue were analyzed, and the expected PRFS error computed. RESULTS: The simulated MR thermometry had maximum single voxel errors ranging between 10% and 18% when no correction was applied. Applying the correction led to a considerable improvement, lowering the maximum error range to 2%-5%. The 5th to 95th percentile interval of the temperature error distribution was also lowered with correction, from approximately 3.5 to 1°C. This correction worked even when T1 times were uniformly raised or lowered by 5%-10%. The experimental data showed predicted errors of 15%. CONCLUSIONS: This simulation study demonstrates that the T1-based correction method reduces MR thermometry errors due to non-local effects from heating in fatty tissues, potentially improving the accuracy of thermometry measurements during MRgFUS treatments. The presented correction method is reliant on having a patient-specific 3D model of the breast, and may be limited by the accuracy of the fat temperatures which in turn may be limited by noise or bias present in the T1 measurements.

Differentiation of symptomatic and asymptomatic carotid intraplaque hemorrhage using 3D high-resolution diffusion-weighted stack of stars imaging.

Ischemic events related to carotid disease are far more strongly associated with plaque instability than stenosis. 3D high-resolution diffusion-weighted (DW) imaging can provide quantitative diffusion measurements on carotid atherosclerosis and may improve detection of vulnerable intraplaque hemorrhage (IPH). The 3D DW-stack of stars (SOS) sequence was implemented with 3D SOS acquisition combined with DW preparation. After simulation of signals created from 3D DW-SOS, phantom studies were performed. Three healthy subjects and 20 patients with carotid disease were recruited. Apparent diffusion coefficient (ADC) values were statistically analyzed on three subgroups by using a two-group comparison Wilcoxon-Mann-Whitney U test with p values less than 0.05: symptomatic versus asymptomatic; IPH-positive versus IPH-negative; and IPH-positive symptomatic versus asymptomatic plaques to determine the relationship with plaque vulnerability. ADC values calculated by 3D DW-SOS provided values similar to those calculated from other techniques. Mean ADC of symptomatic plaque was significantly lower than asymptomatic plaque (0.68 ± 0.18 vs. 0.98 ± 0.16 x 10-3  mm2 /s, p < 0.001). ADC was also significantly lower in IPH-positive versus IPH-negative plaque (0.68 ± 0.13 vs. 1.04 ± 0.11 x 10-3  mm2 /s, p < 0.001). Additionally, ADC was significantly lower in symptomatic versus asymptomatic IPH-positive plaque (0.57 ± 0.09 vs. 0.75 ± 0.11 x 10-3  mm2 /s, p < 0.001). Our results provide strong evidence that ADC measurements from 3D DW-SOS correlate with the symptomatic status of extracranial internal carotid artery plaque. Further, ADC improved discrimination of symptomatic plaque in IPH. These data suggest that diffusion characteristics may improve detection of destabilized plaque leading to elevated stroke risk.

Optimal Carotid Plaque Features on Computed Tomography Angiography Associated With Ischemic Stroke.

Background Stenosis has historically been the major factor used to determine carotid stroke sources. Recent evidence suggests that specific plaque features detected on imaging may be more highly associated with ischemic stroke than stenosis. We sought to determine computed tomography angiography (CTA) imaging features of carotid plaque that optimally discriminate ipsilateral stroke sources. Methods and Results In this institutional review board-approved retrospective cross-sectional study, 494 ipsilateral carotid CTA-brain magnetic resonance imaging pairs were available for analysis after excluding patients with alternative stroke sources. Carotid CTA and clinical markers were recorded, a multivariable Poisson regression model was fitted, and backward elimination was performed with a 2-sided threshold of P<0.10. Discriminatory value was determined using receiver operating characteristic analysis, area under the curve, and bootstrap validation. The final CTA carotid-source stroke prediction model included intraluminal thrombus (prevalence ratio, 2.8 [P<0.001]; 95% CI, 1.6-4.9), maximum soft plaque thickness (prevalence ratio, 1.2 [P<0.001]; 95% CI, 1.1-1.4), and the rim sign (prevalence ratio, 2.0 [P=0.007]; 95% CI, 1.2-3.3). The final discriminatory value (area under the curve=78.3%) was higher than intraluminal thrombus (56.4%, P<0.001), maximum soft plaque thickness (76.4%, P=0.007), or rim sign alone (69.9%, P=0.001). Furthermore, NASCET (North American Symptomatic Carotid Endarterectomy Trial) stenosis categories (cutoffs of 50% and 70%) had lower stroke discrimination (area under the curve=67.4%, P<0.001). Conclusions Optimal discrimination of ipsilateral carotid sources of stroke requires information on intraluminal thrombus, maximum soft plaque thickness, and the rim sign. These results argue against the sole use of carotid stenosis to determine stroke sources on CTA, and instead suggest these alternative markers may better diagnose vulnerable carotid plaque and guide treatment decisions.

Rabbit models of intracranial atherosclerotic disease for pathological validation of vessel wall MRI.

INTRODUCTION: Vessel wall magnetic resonance imaging can improve the evaluation of intracranial atherosclerotic disease. However, pathological validation is needed to improve vessel wall magnetic resonance imaging techniques. Human pathology samples are not practical for such analysis, so an animal model is therefore needed. MATERIALS AND METHODS: Watanabe heritable hyperlipidemic rabbits and apolipoprotein E knockout rabbits were evaluated against New Zealand white wild-type rabbits. Evaluation of intracranial arteries was performed with vessel wall magnetic resonance imaging and pathological analysis, rating the presence and severity of disease in each segment. Two-tailed t-tests were performed to compare disease occurrence and severity prevalence among rabbit subtypes. Sensitivity and specificity were calculated to assess the diagnostic accuracy of vessel wall magnetic resonance imaging. RESULTS: Seventeen rabbits (five Watanabe heritable hyperlipidemic, four apolipoprotein E knockout and eight New Zealand white) were analysed for a total of 51 artery segments. Eleven segments (five Watanabe heritable hyperlipidemic and six apolipoprotein E knockout) demonstrated intracranial atherosclerotic disease on pathology. Disease model animals had lesions more frequently than New Zealand white animals (P<0.001). The sensitivity and specificity of vessel wall magnetic resonance imaging for the detection of intracranial atherosclerotic disease were 68.8% and 95.2%, respectively. When excluding mild cases to assess vessel wall magnetic resonance imaging accuracy for detecting moderate to severe intracranial atherosclerotic disease lesions, sensitivity improved to 100% with unchanged specificity. CONCLUSION: Intracranial atherosclerotic disease can be reliably produced and detected using 3T vessel wall magnetic resonance imaging-compatible Watanabe heritable hyperlipidemic and ApoE rabbit models. Further analysis is needed to characterize better the development and progression of the disease to correlate tissue-validated animal findings with those in human vessel wall magnetic resonance imaging studies.

Magnetic resonance shear wave elastography using transient acoustic radiation force excitations and sinusoidal displacement encoding.

A magnetic resonance (MR) shear wave elastography technique that uses transient acoustic radiation force impulses from a focused ultrasound (FUS) transducer and a sinusoidal-shaped MR displacement encoding strategy is presented. Using this encoding strategy, an analytic expression for calculating the shear wave speed in a heterogeneous medium was derived. Green's function-based simulations were used to evaluate the feasibility of calculating shear wave speed maps using the analytic expression. Accuracy of simulation technique was confirmed experimentally in a homogeneous gelatin phantom. The elastography measurement was compared to harmonic MR elastography in a homogeneous phantom experiment and the measured shear wave speed values differed by less than 14%. This new transient elastography approach was able to map the position and shape of inclusions sized from 8.5 to 14 mm in an inclusion phantom experiment. These preliminary results demonstrate the feasibility of using a straightforward analytic expression to generate shear wave speed maps from MR images where sinusoidal-shaped motion encoding gradients are used to encode the displacement-time history of a transiently propagating wave-packet. This new measurement technique may be particularly well suited for performing elastography before, during, and after MR-guided FUS therapies since the same device used for therapy is also used as an excitation source for elastography.