Elizabeth Ramsay

Differences in Natural History between Breast Cancers in BRCA1 and BRCA2 Mutation Carriers and Effects of MRI Screening-MRISC, MARIBS, and Canadian Studies Combined

Background: It is recommended that BRCA1/2 mutation carriers undergo breast cancer screening using MRI because of their very high cancer risk and the high sensitivity of MRI in detecting invasive cancers. Clinical observations suggest important differences in the natural history between breast cancers due to mutations in BRCA1 and BRCA2, potentially requiring different screening guidelines. Methods: Three studies of mutation carriers using annual MRI and mammography were analyzed. Separate natural history models for BRCA1 and BRCA2 were calibrated to the results of these studies and used to predict the impact of various screening protocols on detection characteristics and mortality. Results: BRCA1/2 mutation carriers (N = 1,275) participated in the studies and 124 cancers (99 invasive) were diagnosed. Cancers detected in BRCA2 mutation carriers were smaller [80% ductal carcinoma in situ (DCIS) or ≤10 mm vs. 49% for BRCA1, P < 0.001]. Below the age of 40, one (invasive) cancer of the 25 screen-detected cancers in BRCA1 mutation carriers was detected by mammography alone, compared with seven (three invasive) of 11 screen-detected cancers in BRCA2 (P < 0.0001). In the model, the preclinical period during which cancer is screen-detectable was 1 to 4 years for BRCA1 and 2 to 7 years for BRCA2. The model predicted breast cancer mortality reductions of 42% to 47% for mammography, 48% to 61% for MRI, and 50% to 62% for combined screening. Conclusions: Our studies suggest substantial mortality benefits in using MRI to screen BRCA1/2 mutation carriers aged 25 to 60 years but show important clinical differences in natural history. Impact: BRCA1 and BRCA2 mutation carriers may benefit from different screening protocols, for example, below the age of 40. Cancer Epidemiol Biomarkers Prev; 21(9); 1458–68. ©2012 AACR.

MR thermometry in the human prostate gland at 3.0T for transurethral ultrasound therapy

To investigate the spatial, temporal, and temperature resolution of a segmented gradient echo echo‐planar imaging (EPI) technique as applied to proton resonance frequency (PRF) shift thermometry at 3 T in the human prostate gland, and to determine appropriate sequence parameters for magnetic resonance imaging (MRI)‐controlled transurethral ultrasound thermal therapy.

Incorporating endorectal MR elastography into multi-parametric MRI for prostate cancer imaging: Initial feasibility in volunteers

To investigate the tolerability and technical feasibility of performing endorectal MR elastography (eMRE) in human volunteers within the representative age group commonly affected by prostate cancer.

Temperature-dependent MR signals in cortical bone: Potential for monitoring temperature changes during high-intensity focused ultrasound treatment in bone

Because existing magnetic resonance thermometry techniques do not provide temperature information within bone, high‐intensity focused ultrasound (HIFU) exposures in bone are monitored using temperature changes in adjacent soft tissues. In this study, the potential to monitor temperature changes in cortical bone using a short TE gradient echo sequence is evaluated.

Comparison of biphasic and reordered fat suppression for dynamic breast MRI

To optimize a reordered k‐space acquisition that applies intermittent fat saturation (FS) pulses to allow for a time‐efficient reduction of fat signal in breast MR images, and compare it with an elliptic‐centric biphasic FS method in terms of the degree of fat suppression and speed.

Evaluation of Focal Ablation of Magnetic Resonance Imaging Defined Prostate Cancer Using Magnetic Resonance Imaging Controlled Transurethral Ultrasound Therapy with Prostatectomy as the Reference Standard

Purpose: We evaluated magnetic resonance imaging controlled transurethral ultrasound therapy as a treatment for magnetic resonance imaging defined focal prostate cancer using subsequent prostatectomy and histology as the reference standard. Materials and Methods: Five men completed this pilot study, which was approved by the institutional review board. Prior to radical prostatectomy focal tumors identified by magnetic resonance imaging were treated by coagulating targeted subtotal 3‐dimensional volumes of prostate tissue using magnetic resonance imaging controlled transurethral focused ultrasound. Treatment was performed with a 3 Tesla clinical magnetic resonance imaging unit combined with modified clinical planning software for high intensity focused ultrasound therapy. After prostatectomy whole mount histological sections parallel to the magnetic resonance imaging treatment planes were used to compare magnetic resonance imaging measurements with thermal damage at the cellular level and, thus, evaluate treatment and target accuracy. Results: Three‐dimensional target volumes of 4 to 20 cc and with radii up to 35 mm from the urethra were treated successfully. Mean ± SD temperature control accuracy at the target boundary was −1.6 ± 4.8C and the mean spatial targeting accuracy achieved was −1.5 ± 2.8 mm. Mean treatment accuracy with respect to histology was −0.4 ± 1.7 mm with all index tumors falling inside the histological outer limit of thermal injury. Conclusions: Magnetic resonance imaging guided transurethral ultrasound therapy is capable of generating thermal coagulation and tumor destruction in targeted 3‐dimensional angular sectors out to the prostate capsule for prostate glands up to 70 cc in volume. Ultrasound parameters needed to achieve ablation at the prostate capsule were determined, providing a foundation for future studies.

Influence of geometric and material properties on artifacts generated by interventional MRI devices

PURPOSE Magnetic resonance imaging (MRI) is capable of providing valuable real-time feedback during medical procedures, partly due to the excellent soft-tissue contrast available. Several technical hurdles still exist to seamless integration of medical devices with MRI due to incompatibility of most conventional devices with this imaging modality. In this study, the effect of local perturbations in the magnetic field caused by the magnetization of medical devices was examined using finite element analysis modeling. As an example, the influence of the geometric and material characteristics of a transurethral high-intensity ultrasound applicator on temperature measurements using proton resonance frequency (PRF)-shift thermometry was investigated. METHODS The effect of local perturbations in the magnetic field, caused by the magnetization of medical device components, was examined using finite element analysis modeling. The thermometry artifact generated by a transurethral ultrasound applicator was simulated, and these results were validated against analytic models and scans of an applicator in a phantom. Several parameters were then varied to identify which most strongly impacted the level of simulated thermometry artifact, which varies as the applicator moves over the course of an ablative high-intensity ultrasound treatment. RESULTS Key design parameters identified as having a strong influence on the magnitude of thermometry artifact included the susceptibility of materials and their volume. The location of components was also important, particularly when positioned to maximize symmetry of the device. Finally, the location of component edges and the inclination of the device relative to the magnetic field were also found to be important factors. CONCLUSIONS Previous design strategies to minimize thermometry artifact were validated, and novel design strategies were identified that substantially reduce PRF-shift thermometry artifacts for a variety of device orientations. These new strategies are being incorporated into the next generation of applicators. The general strategy described in this study can be applied to the design of other interventional devices intended for use with MRI.

Influence of geometric and material properties on artifacts generated by interventional MRI devices: Relevance to PRF-shift thermometry

PURPOSE Magnetic resonance imaging (MRI) is capable of providing valuable real-time feedback during medical procedures, partly due to the excellent soft-tissue contrast available. Several technical hurdles still exist to seamless integration of medical devices with MRI due to incompatibility of most conventional devices with this imaging modality. In this study, the effect of local perturbations in the magnetic field caused by the magnetization of medical devices was examined using finite element analysis modeling. As an example, the influence of the geometric and material characteristics of a transurethral high-intensity ultrasound applicator on temperature measurements using proton resonance frequency (PRF)-shift thermometry was investigated. METHODS The effect of local perturbations in the magnetic field, caused by the magnetization of medical device components, was examined using finite element analysis modeling. The thermometry artifact generated by a transurethral ultrasound applicator was simulated, and these results were validated against analytic models and scans of an applicator in a phantom. Several parameters were then varied to identify which most strongly impacted the level of simulated thermometry artifact, which varies as the applicator moves over the course of an ablative high-intensity ultrasound treatment. RESULTS Key design parameters identified as having a strong influence on the magnitude of thermometry artifact included the susceptibility of materials and their volume. The location of components was also important, particularly when positioned to maximize symmetry of the device. Finally, the location of component edges and the inclination of the device relative to the magnetic field were also found to be important factors. CONCLUSIONS Previous design strategies to minimize thermometry artifact were validated, and novel design strategies were identified that substantially reduce PRF-shift thermometry artifacts for a variety of device orientations. These new strategies are being incorporated into the next generation of applicators. The general strategy described in this study can be applied to the design of other interventional devices intended for use with MRI.

Dual echo gradient echo imaging for simultaneous thermal mapping in cortical bone and soft tissue

MRI-guided high-intensity focused ultrasound (MR-HIFU) therapy can relieve pain associated with metastatic and benign bone tumours in patients who fail to respond to conventional radiation therapy. However, since existing MR-thermometry techniques do not provide temperature information within the bone, HIFU exposures in bone are currently monitored using temperature changes in adjacent soft tissues. In this study, a standard dual echo spoiled gradient echo (SPGR) sequence is proposed to monitor thermal effects in both bone and soft tissue simultaneously. Magnitude signal changes at the shorter TE (~1ms) reflect thermal changes in cortical bone, while phase changes at the longer TE (~10ms) allow conventional PRF thermometry in surrounding tissues.

Dual-frequency ultrasound focal therapy for MRI-guided transurethral treatment of the prostate: Study in gel phantom

Ultrasound thermal therapy of localized prostate cancer offers a minimally-invasive non-ionizing alternative [1-3] to surgery and radiotherapy. MRI-controlled transurethral ultrasound prostate therapy [4-6] has previously been investigated in a pilot human feasibility study [7], by treating a small sub-volume of prostate tissue. In this study, the feasibility of transurethral dual-frequency ultrasound focal therapy has been investigated in gel phantom. A database of pelvic anatomical models of human prostate cancer patients have been created using MR clinical images. The largest prostate boundary (47 cm3) was used to fabricate an anatomical gel phantom which included various MR characteristics to mimic prostate tissues, 4 localized tumors and surrounding prostate tissues. A 9-element transurethral ultrasound applicator working in dual-frequency mode (f = 4.6/14.5 MHz) was evaluated to heat: (i) the entire prostate volume (Full prostate treatment strategy), (ii) a prostate region restricted to tumors (Foca...