Kim Butts-Pauly

Quantifying the local tissue volume and composition in individual brains with magnetic resonance imaging

Here, we describe a quantitative neuroimaging method to estimate the macromolecular tissue volume (MTV), a fundamental measure of brain anatomy. By making measurements over a range of field strengths and scan parameters, we tested the key assumptions and the robustness of the method. The measurements confirm that a consistent quantitative estimate of MTV can be obtained across a range of scanners. MTV estimates are sufficiently precise to enable a comparison between data obtained from an individual subject with control population data. We describe two applications. First, we show that MTV estimates can be combined with T1 and diffusion measurements to augment our understanding of the tissue properties. Second, we show that MTV provides a sensitive measure of disease status in individual patients with multiple sclerosis. The MTV maps are obtained using short clinically appropriate scans that can reveal how tissue changes influence behavior and cognition.

Capacitive Micromachined Ultrasonic Transducers for Therapeutic Ultrasound Applications

Therapeutic ultrasound guided by MRI is a noninvasive treatment that potentially reduces mortality, lowers medical costs, and widens accessibility of treatments for patients. Recent developments in the design and fabrication of capacitive micromachined ultrasonic transducers (CMUTs) have made them competitive with piezoelectric transducers for use in therapeutic ultrasound applications. In this paper, we present the first designs and prototypes of an eight-element, concentric-ring, CMUT array to treat upper abdominal cancers. This array was simulated and designed to focus 30-50 mm into tissue, and ablate a 2- to 3-cm-diameter tumor within 1 h. Assuming a surface acoustic output pressure of 1 MPa peak-to-peak (8.5 W/cm2) at 2.5 MHz, we simulated an array that produced a focal intensity of 680 W/cm2 when focusing to 35 mm. CMUT cells were then designed to meet these frequency and surface acoustic intensity specifications. These cell designs were fabricated as 2.5 mm x 2.5 mm test transducers and used to verify our models. The test transducers were shown to operate at 2.5 MHz with an output pressure of 1.4 MPa peak-to-peak (16.3 W/cm2). With this CMUT cell design, we fabricated a full eight-element array. Due to yield issues, we only developed electronics to focus the four center elements of the array. The beam profile of the measured array deviated from the simulated one because of the crosstalk effects; the beamwidth matched within 10% and sidelobes increased by two times, which caused the measured gain to be 16.6 compared to 27.4.

MRI‐guided radiofrequency ablation of breast cancer: Preliminary clinical experience

This study was designed to demonstrate the feasibility of MRI‐guided radiofrequency ablation (RFA) of breast cancer. A total of three women diagnosed with invasive ductal breast cancer were treated with percutaneous MRI‐guided RFA, according to a treat and resect protocol, in our hospital. RFA procedures were performed in an open 0.5T Signa‐SP imager allowing direct patient access and real‐time monitoring of the procedure. In all patients ablation was performed with a 15‐gauge insulated MRI‐compatible multiple needle probe. MRI thermometry and contrast‐enhanced postablation MRI were used to evaluate the ablation process. Patients underwent lumpectomy within a week of the RFA procedure. Histopathology confirmed successful (100%) tumor ablation in one patient, and partial tumor destruction (33% and 50%, respectively) in two patients. Challenges of MRI‐guided breast RFA that need to be solved to facilitate progress of the technique toward clinical practice are discussed. J. Magn. Reson. Imaging 2007.

Reweighted ℓ1 Referenceless PRF Shift Thermometry

Temperature estimation in proton resonance frequency (PRF) shift MR thermometry requires a reference, or pretreatment, phase image that is subtracted from image phase during thermal treatment to yield a phase difference image proportional to temperature change. Referenceless thermometry methods derive a reference phase image from the treatment image itself by assuming that in the absence of a hot spot, the image phase can be accurately represented in a smooth (usually low order polynomial) basis. By masking the hot spot out of a least squares (ℓ2) regression, the reference phase images coefficients on the polynomial basis are estimated and a reference image is derived by evaluating the polynomial inside the hot spot area. Referenceless methods are therefore insensitive to motion and bulk main field shifts, however, currently these methods require user interaction or sophisticated tracking to ensure that the hot spot is masked out of the polynomial regression. This article introduces an approach to reference PRF shift thermometry that uses reweighted ℓ1 regression, a form of robust regression, to obtain background phase coefficients without hot spot tracking and masking. The method is compared to conventional referenceless thermometry, and demonstrated experimentally in monitoring HIFU heating in a phantom and canine prostate, as well as in a healthy human liver. Magn Reson Med, 2010.

Evaluation of wafer bonded CMUTs with rectangular membranes featuring high fill factor

Increasing fill factor is one design approach used to increase average output displacement, output pressure, and sensitivity of capacitive micromachined ultrasonic transducers (CMUTs). For rectangular cells, the cell-to-cell spacing and the aspect ratio determine the fill factor. In this paper, we explore the effects of these parameters on performance, in particular the nonuniformity of collapse voltage between neighboring cells and presence of higher order modes in air or immersed operation. We used a white light interferometer to measure nonuniformity in deflection between neighboring cells. We found that reducing the cell-to-cell spacing could cause bending of the center support post, which amplifies nonuniformities in collapse voltage to 18.4% between neighboring cells. Using a 2-D finite element model (FEM), we found that for our designs, increasing the support post width to 1.67 times the membrane thickness alleviated the post bending problem. Using impedance and interferometer measurements to observe the effects of aspect ratio on higher order modes, we found that the (1,3) modal frequency approached the (1,1) modal frequency as the aspect ratio of the rectangles increased. In air operation, under continuous wave (CW) excitation at the center frequency, the rectangular cells behaved in the (1,1) mode. In immersion, because of dispersive guided modes, these cells operated in a higher order mode when excited with a CW signal at the center frequency. This contributed to a loss of output pressure; for this reason our rectangular design was unsuitable for CW operation in immersion.

Prospective motion correction using tracking coils

Intracavity imaging coils provide higher signal‐to‐noise than surface coils and have the potential to provide higher spatial resolution in shorter acquisition times. However, images from these coils suffer from physiologically induced motion artifacts, as both the anatomy and the coils move during image acquisition. We developed prospective motion‐correction techniques for intracavity imaging using an array of tracking coils. The system had <50 ms latency between tracking and imaging, so that the images from the intracavity coil were acquired in a frame of reference defined by the tracking array rather than by the systems gradient coils. Two‐dimensional gradient‐recalled and three‐dimensional electrocardiogram‐gated inversion‐recovery‐fast‐gradient‐echo sequences were tested with prospective motion correction using ex vivo hearts placed on a moving platform simulating both respiratory and cardiac motion. Human abdominal tests were subsequently conducted. The tracking array provided a positional accuracy of 0.7 ± 0.5 mm, 0.6 ± 0.4 mm, and 0.1 ± 0.1 mm along the X, Y, and Z directions at a rate of 20 frames‐per‐second. The ex vivo and human experiments showed significant image quality improvements for both in‐plane and through‐plane motion correction, which although not performed in intracavity imaging, demonstrates the feasibility of implementing such a motion‐correction system in a future design of combined tracking and intracavity coil. Magn Reson Med, 2013.

P1B-10 Advantages of Capacitive Micromachined Ultrasonics Transducers (CMUTs) for High Intensity Focused Ultrasound (HIFU)

In the past ten years, high intensity focused ultrasound (HIFU) has become popular for minimally invasive and non-invasive therapies. Traditionally piezoelectric transducers have been used for HIFU applications, but capacitive micro- machined ultrasonic transducers (CMUTs) have been shown to have advantages, including ease of fabrication and efficient performance. In this paper, we show the fabrication and testing of CMUTs specifically designed for HIFU. We compare the operation of these designs with finite element models. In addition, we demonstrate that CMUTs can operate under high pressure and continuous wave (CW) conditions, with minimal self-heating, a problem that piezoelectric transducers often face. Finally, we demonstrate MR-temperature monitoring of the heating created by an unfocused HIFU CMUT.

MR imaging-guided percutaneous cryoablation of the prostate in an animal model: in vivo imaging of cryoablation-induced tissue necrosis with immediate histopathologic correlation.

PURPOSE To evaluate the feasibility of magnetic resonance (MR) imaging-guided percutaneous cryoablation of normal canine prostates and to identify MR imaging features that accurately predict the area of tissue damage at a microscopic level. MATERIALS AND METHODS Six adult male mixed-breed dogs were anesthetized, intubated, and placed in a 0.5-T open MR imaging system. A receive-only endorectal coil was placed, and prostate location and depth were determined on T1-weighted fast spin-echo (FSE) MR imaging. After placement of cryoprobes and temperature sensors, three freezing protocols were used to ablate prostate tissue. Ice ball formation was monitored with T1-weighted FSE imaging. Tissue necrosis area was assessed with contrast-enhanced weighted MR imaging and compared with histopathologic findings. RESULTS A total of 12 cryolesions (mean size, 1.2 cm) were bilaterally created in six prostates. Ice ball formation was oval and signal-free on T1-weighted FSE sequences in all cases. Postprocedural contrast-enhanced MR imaging typically showed a nonenhancing area of low signal intensity centrally located within the frozen area, surrounded by a bright enhancing rim in all cases. On histopathologic examination, two distinct zones were identified within cryolesions. Centrally, a necrotic zone with complete cellular destruction and hemorrhage was found. Between this necrotic zone and normal glandular tissue, a zone of fragmented and intact glands, interstitial edema, and rare acute inflammatory cells was seen. Correlation between nonenhancement on contrast-enhanced weighted MR images and tissue necrosis on pathologic examination was consistent within all six dogs. CONCLUSIONS MR imaging-guided cryoablation of the prostate is technically feasible. The nonenhancing area on postablation contrast-enhanced weighted MR imaging accurately predicts the area of cryoablation-induced tissue necrosis on pathologic analysis.

Is MR-guided High-intensity Focused Ultrasound a Feasible Treatment Modality for Desmoid Tumors?

BackgroundMR-guided high-intensity focused ultrasound is a noninvasive treatment modality that uses focused ultrasound waves to thermally ablate tumors within the human body while minimizing side effects to surrounding healthy tissues. This technology is FDA-approved for certain tumors and has potential to be a noninvasive treatment option for extremity soft tissue tumors. Development of treatment modalities that achieve tumor control, decrease morbidity, or both might be of great benefit for patients. We wanted to assess the potential use of this technology in the treatment of extremity desmoid tumors.Questions/purposes(1) Can we use MR-guided high-intensity focused ultrasound to accurately ablate a predetermined target volume within a human cadaver extremity? (2) Does MR-guided high-intensity focused ultrasound treatment stop progression and/or cause regression of extremity desmoid tumors?MethodsSimulated tumor volumes in four human cadavers, created by using plastic markers, were ablated using a commercially available focused ultrasound system. Accuracy was determined in accordance with the International Organization of Standards location error by measuring the farthest distance between the ablated tissue and the plane corresponding to the target. Between 2012 and 2014, we treated nine patients with desmoid tumors using focused ultrasound ablation. Indications for this were tumor-related symptoms or failure of conventional treatment. Of those, five of them were available for MRI followup at 12 months or longer (mean, 18.2 months; range, 12–23 months). The radiographic and clinical outcomes of five patients who had desmoid tumors treated with focused ultrasound were prospectively recorded. Patients were assessed preoperatively with MRI and followed at routine intervals after treatment with MRI scans and clinical examination.ResultsThe ablation accuracy for the four cadaver extremities was 5 mm, 3 mm, 8 mm, and 8 mm. Four patients’ tumors became smaller after treatment and one patient has slight progression at the time of last followup. The mean decrease in tumor size determined by MRI measurements was 36% (95% confidence interval, 7%–66%). No patient has received additional adjuvant systemic or local treatment. Treatment-related adverse events included first- and second-degree skin burns occurring in four patients, which were managed successfully without further surgery.ConclusionsThis preliminary investigation provides some evidence that MR-guided high-intensity focused ultrasound may be a feasible treatment for desmoid tumors. It may also be of use for other soft tissue neoplasms in situations in which there are limited traditional treatment options such as recurrent sarcomas. Further investigation is necessary to better define the indications, efficacy, role, and long-term oncologic outcomes of focused ultrasound treatment.Level of EvidenceLevel IV, therapeutic study.

1I-2 Capacitive Micromachined Ultrasonic Transducers for High Intensity Focused Ablation of Upper Abdominal Tumors

We present the development of a capacitive micromachined ultrasonic transducer (CMUT) array for noninvasive focused ultrasound ablation of lower abdominal cancers under MR-guidance. While piezoelectric transducers have been traditionally used for high intensity focused ultrasound (HIFU), recent advances in capacitive micromachined ultrasonic transducers (CMUTs) have made them highly competitive with regard to costs, fabrication flexibility, and performance. Even current imaging CMUTs have shown capability of HIFU operation through high power and continuous wave operation. In this paper, we will show our experiments with current imaging CMUTs operated in HIFU mode. In addition, we will show the design and development of CMUT membranes and a transducer array specifically for HIFU ablation lower abdominal cancers