Correlation between the temperature dependence of intrinsic MR parameters and thermal dose measured by a rapid chemical shift imaging technique.

In order to investigate simultaneous MR temperature imaging and direct validation of tissue damage during thermal therapy, temperature-dependent signal changes in proton resonance frequency (PRF) shifts, R(2)* values, and T1-weighted amplitudes are measured from one technique in ex vivo tissue. Using a multigradient echo acquisition and the Stieglitz-McBride algorithm, the temperature sensitivity coefficients of these parameters are measured in each tissue at high spatiotemporal resolutions (1.6 x 1.6 x 4 mm 3,≤ 5sec) at the range of 25-61 °C. Non-linear changes in MR parameters are examined and correlated with an Arrhenius rate dose model of thermal damage. Using logistic regression, the probability of changes in these parameters is calculated as a function of thermal dose to determine if changes correspond to thermal damage. Temperature sensitivity of R(2)* and, in some cases, T1-weighted amplitudes are statistically different before and after thermal damage occurred. Significant changes in the slopes of R(2)* as a function of temperature are observed. Logistic regression analysis shows that these changes could be accurately predicted using the Arrhenius rate dose model (Ω = 1.01 ± 0.03), thereby showing that the changes in R(2)* could be direct markers of protein denaturation. Overall, by using a chemical shift imaging technique with simultaneous temperature estimation, R(2)* mapping and T1-W imaging, it is shown that changes in the sensitivity of R(2)* and, to a lesser degree, T1-W amplitudes are measured in ex vivo tissue when thermal damage is expected to occur. These changes could possibly be used for direct validation of thermal damage in contrast to model-based predictions.

A national case-control study of risk factors for listeriosis in Australia.

Listeriosis is a foodborne disease associated with significant mortality. This study attempts to identify risk factors for sporadic listeriosis in Australia. Information on underlying illnesses was obtained from cases' treating doctors and other risk factors were elicited from the patient or a surrogate. We attempted to recruit two controls per case matched on age and primary underlying immune condition. Between November 2001 and December 2004 we recruited 136 cases and 97 controls. Of perinatal cases, living in a household where a language other than English was spoken was the main risk factor associated with listeriosis (OR 11·3, 95% CI 1·5-undefined). Of non-perinatal cases we identified the following risk factors for listeriosis: prior hospitalization (OR 4·3, 95% CI 1·0-18·3), use of gastric acid inhibitors (OR 9·4, 95% CI 2·4-37·4), and consumption of camembert (OR 4·7, 95% CI 1·1-20·6). Forty percent of cases with prior hospitalization were exposed to high-risk foods during hospitalization.

Magnetic resonance temperature imaging validation of a bioheat transfer model for laser-induced thermal therapy.

PURPOSE: Magnetic resonance-guided laser-induced thermal therapy (MRgLITT) is currently undergoing initial safety and feasibility clinical studies for the treatment of intracranial lesions in humans. As studies progress towards evaluation of treatment efficacy, predictive computational models may play an important role for prospective 3D treatment planning. The current work critically evaluates a computational model of laser induced bioheat transfer against retrospective multiplanar MR thermal imaging (MRTI) in a canine model of the MRgLITT procedure in the brain. METHODS: A 3D finite element model of the bioheat transfer that couples Pennes equation to a diffusion theory approximation of light transport in tissue is used. The laser source is modelled conformal with the applicator geometry. Dirichlet boundary conditions are used to model the temperature of the actively cooled catheter. The MRgLITT procedure was performed on n = 4 canines using a 1-cm diffusing tip 15-W diode laser (980 nm). A weighted L2norm is used as the metric of comparison between the spatiotemporal MR-derived temperature estimates and model prediction. RESULTS: The normalised error history between the computational models and MRTI was within 1-4 standard deviations of MRTI noise. Active cooling models indicate that the applicator temperature has a strong effect on the maximum temperature reached, but does not significantly decrease the tissue temperature away from the active tip. CONCLUSIONS: Results demonstrate the computational model of the bioheat transfer may provide a reasonable approximation of the laser-tissue interaction, which could be useful for treatment planning, but cannot readily replace MR temperature imaging in a complex environment such as the brain.

Dynamic Contrast-Enhanced MRI in Patients with Brain Metastases Undergoing Laser Interstitial Thermal Therapy: A Pilot Study.

BACKGROUND AND PURPOSE: Tumor recurrence is difficult to predict in patients receiving laser ablation for intracranial malignancy. We assessed the efficacy of the initial area under the time-to-signal intensity curve at 60 seconds (iAUC60) from dynamic contrast-enhanced MR imaging in predicting progression-free survival in patients with brain metastases following laser interstitial thermal therapy. MATERIALS AND METHODS: The study population was a consecutive series of patients undergoing laser interstitial thermal therapy for brain metastases. Patient demographics including age, sex, tumor histology, and Karnofsky Performance Scale were collected prospectively. Preoperative, postoperative, and 1-month follow-up dynamic contrast-enhanced MRIs were analyzed. Values of iAUC60 were computed using a trapezoidal rule applied to the time history of contrast uptake over the first 60 seconds postenhancement. The change in iAUC60 (ΔiAUC60) was calculated by taking the difference between the values of iAUC60 from 2 time points. Pearson correlation coefficients were calculated between progression-free survival, defined as the time from laser interstitial thermal therapy to tumor recurrence, and iAUC60 or ΔiAUC60 values. RESULTS: Thirty-three cases of laser interstitial thermal therapy for 32 brain metastases in a cohort of 27 patients were prospectively analyzed. A significant relationship was observed between the values of iAUC60 from postoperative dynamic contrast-enhanced MR imaging and progression-free survival with Pearson correlation (P = .03) and Cox univariate analysis (P = .01). The relationship between preoperative and 1-month follow-up dynamic contrast-enhanced MR imaging was not significantly correlated with progression-free survival. Similarly, no statistically significant relationship was observed with ΔiAUC60 and progression-free survival between any time points. CONCLUSIONS: Progression-free survival is difficult to predict in patients undergoing laser interstitial thermal therapy for brain metastases due to confounding with posttreatment change. iAUC60 extracted from postoperative dynamic contrast-enhanced MR imaging shows promise for accurately prognosticating patients following this operative therapy.

Dynamic Data-Driven Finite Element Models for Laser Treatment of Cancer.

Elevating the temperature of cancerous cells is known to increase their susceptibility to subsequent radiation or chemotherapy treatments, and in the case in which a tumor exists as a well-defined region, higher intensity heat sources may be used to ablate the tissue. These facts are the basis for hyperthermia based cancer treatments. Of the many available modalities for delivering the heat source, the application of a laser heat source under the guidance of real-time treatment data has the potential to provide unprecedented control over the outcome of the treatment process [7, 18]. The goals of this work are to provide a precise mathematical framework for the real-time finite element solution of the problems of calibration, optimal heat source control, and goal-oriented error estimation applied to the equations of bioheat transfer and demonstrate that current finite element technology, parallel computer architecture, data transfer infrastructure, and thermal imaging modalities are capable of inducing a precise computer controlled temperature field within the biological domain.

Prostate magnetic resonance imaging for brachytherapists: Anatomy and technique.

PURPOSE: To present an overview of mp MRI techniques necessary for high-resolution imaging of prostate. METHODS: We summarize examples from our clinical experience and concepts from the current literature that illustrate normal prostate anatomy on multiparametric MRI (mp MRI). RESULTS: Our experience regarding optimal mp MRI image acquisition is provided, as well as a summary of prostate and periprostatic anatomy and anatomical variants that pose challenges for BT. CONCLUSIONS: mp MRI provides unparalleled assessment of the prostate and periprostatic anatomy, making it the most appropriate imaging modality to facilitate prostate BT treatment planning, implantation, and followup. This work provides an introduction to prostate mp MR imaging, anatomy, and anatomical variants essential for successful integration mp MRI into prostate brachytherapy practice.

Prostate magnetic resonance imaging for brachytherapists: Diagnosis, imaging pitfalls, and post-therapy assessment.

Optimal integration of multiparametric MRI (mp MRI) into prostate brachytherapy practice necessitates an understanding of imaging findings pertinent to prostate cancer detection and staging. This review will summarize prostate cancer imaging findings and tumor staging on mp MRI, including an overview of the Prostate Imaging Reporting and Data System (PIRADS)-structured reporting schema, mp MRI findings observed in the post-therapy setting including cases of post-treatment recurrence, and MRI concepts integral to successful salvage brachytherapy.

Accelerated magnetic resonance thermometry in the presence of uncertainties.

A model-based information theoretic approach is presented to perform the task of magnetic resonance (MR) thermal image reconstruction from a limited number of observed samples on k-space. The key idea of the proposed approach is to optimally detect samples of k-space that are information-rich with respect to a model of the thermal data acquisition. These highly informative k-space samples can then be used to refine the mathematical model and efficiently reconstruct the image. The information theoretic reconstruction was demonstrated retrospectively in data acquired during MR-guided laser induced thermal therapy (MRgLITT) procedures. The approach demonstrates that locations with high-information content with respect to a model-based reconstruction of MR thermometry may be quantitatively identified. These information-rich k-space locations are demonstrated to be useful as a guide for k-space undersampling techniques. The effect of interactively increasing the predicted number of data points used in the subsampled model-based reconstruction was quantified using the L2-norm of the distance between the subsampled and fully sampled reconstruction. Performance of the proposed approach was also compared with uniform rectilinear subsampling and variable-density Poisson disk subsampling techniques. The proposed subsampling scheme resulted in accurate reconstructions using a small fraction of k-space points, suggesting that the reconstruction technique may be useful in improving the efficiency of thermometry data temporal resolution.

Transurethral ultrasound applicators with directional heating patterns for prostate thermal therapy: in vivo evaluation using magnetic resonance thermometry.

A catheter-based transurethral ultrasound applicator with angularly directional heating patterns has been designed for prostate thermal therapy and evaluated in canine prostate in vivo using MRI to monitor and assess performance. The ultrasound transducer array (3.5 mm diameter tubular transducers, 180 degrees active sectors, approximately 7.5 MHz) was integrated to a flexible delivery catheter (4 mm OD), and encapsulated within an expandable balloon (35 mm x 10 mm OD, 80 ml min(-1) ambient water) for coupling and cooling of the prostatic urethra. These devices were used to thermally coagulate targeted portions of the canine prostate (n = 2) while using MR thermal imaging (MRTI) to monitor the therapy. MRI was also used for target definition, positioning of the applicator, and evaluation of target viability post-therapy. MRTI was based upon the complex phase-difference mapping technique using an interleaved gradient echo-planar imaging sequence with lipid suppression. MRTI derived temperature distributions, thermal dose exposures, T1-contrast enhanced MR images, and histology of sectioned prostates were used to define destroyed tissue zones and characterize the three-dimensional heating patterns. The ultrasound applicators produced approximately 180 degrees directed zones of thermal coagulation within targeted tissue which extended 15-20 mm radially to the outer boundary of the prostate within 15 min. Transducer activation lengths of 17 mm and 24 mm produced contiguous zones of coagulation extending axially approximately 18 mm and approximately 25 mm from base to apex, respectively. Peak temperatures around 90 degrees C were measured, with approximately 50 degrees C-52 degrees C corresponding to outer boundary t43 = 240 min at approximately 15 min treatment time. These devices are MRI compatible, and when coupled with multiplanar MRTI provide a means for selectively controlling the length and sector angle of therapeutic thermal treatment in the prostate.

The feasibility of elastographic visualization of HIFU-induced thermal lesions in soft tissues. Image-guided high-intensity focused ultrasound.

The potential for visualizing high-intensity focused ultrasound (HIFU)-induced thermal lesions in biological soft tissues in vitro using elastography was investigated. Thermal lesions were created in rabbit paraspinal skeletal muscle in vivo. The rabbits were sacrificed 60 h following the treatment and lesioned tissues were excised. The tissues were cast in a block of clear gel and elastographic images of the lesions were acquired. Gross pathology of the tissue samples confirmed the characteristics of the lesions.

Elastographic imaging of thermal lesions in soft tissue: a preliminary study in vitro.

The use of elastography for the visualization of thermal lesions in biological soft tissue in vitro was investigated. Thermal lesions were created in samples of postmortem ovine kidney using a surgical neodymium: YAG (Nd:YAG) laser. The kidney samples were cast in gel, and elastographic images of the lesions were constructed using sonographic information and external markers to locate the region of interest. Gross pathology of the kidney samples confirmed the dimensions of the lesions. Good correlation between the lesion length along the laser fiber axis and maximum diameter measured off of the fiber axis determined from elastographic images and gross pathology photographs was found.

Elastographic characterization of HIFU-induced lesions in canine livers.

The elastographic visualization and evaluation of high-intensity focused ultrasound (HIFU)-induced lesions were investigated. The lesions were induced in vitro in freshly excised canine livers. The use of different treatment intensity levels and exposure times resulted in lesions of different sizes. Each lesion was clearly depicted by the corresponding elastogram as being an area harder than the background. The strain contrast of the lesion/background was found to be dependent on the level of energy deposition. A lesion/background strain contrast between -2.5 dB and -3.5 dB was found to completely define the entire zone of tissue damage. The area of tissue damage was automatically estimated from the elastograms by evaluating the number of pixels enclosed inside the isointensity contour lines corresponding to a strain contrast of -2.5, -3 and -3.5 dB. The area of the lesion was measured from a tissue photograph obtained at approximately the same plane where elastographic data were collected. The estimated lesion areas ranged between approximately 10 mm2 and 110 mm2. A high correlation between the damaged areas as depicted by the elastograms and the corresponding areas as measured from the gross pathology photographs was found (r2 = 0.93, p value < 0.0004, n = 16). This statistically significant high correlation demonstrates that elastography has the potential to become a reliable and accurate modality for HIFU therapy monitoring.

Design and initial evaluation of a treatment planning software system for MRI-guided laser ablation in the brain.

PURPOSE: An open-source software system for planning magnetic resonance (MR)-guided laser-induced thermal therapy (MRgLITT) in brain is presented. The system was designed to provide a streamlined and operator-friendly graphical user interface (GUI) for simulating and visualizing potential outcomes of various treatment scenarios to aid in decisions on treatment approach or feasibility. METHODS: A portable software module was developed on the 3D Slicer platform, an open-source medical imaging and visualization framework. The module introduces an interactive GUI for investigating different laser positions and power settings as well as the influence of patient-specific tissue properties for quickly creating and evaluating custom treatment options. It also provides a common treatment planning interface for use by both open-source and commercial finite element solvers. In this study, an open-source finite element solver for Pennes' bioheat equation is interfaced to the module to provide rapid 3D estimates of the steady-state temperature distribution and potential tissue damage in the presence of patient-specific tissue boundary conditions identified on segmented MR images. RESULTS: The total time to initialize and simulate an MRgLITT procedure using the GUI was [Formula: see text]5 min. Each independent simulation took [Formula: see text]30 s, including the time to visualize the results fused with the planning MRI. For demonstration purposes, a simulated steady-state isotherm contour [Formula: see text] was correlated with MR temperature imaging (N = 5). The mean Hausdorff distance between simulated and actual contours was 2.0 mm [Formula: see text], whereas the mean Dice similarity coefficient was 0.93 [Formula: see text]. CONCLUSIONS: We have designed, implemented, and conducted initial feasibility evaluations of a software tool for intuitive and rapid planning of MRgLITT in brain. The retrospective in vivo dataset presented herein illustrates the feasibility and potential of incorporating fast, image-based bioheat predictions into an interactive virtual planning environment for such procedures.

An inverse problem approach to recovery of in vivo nanoparticle concentrations from thermal image monitoring of MR-guided laser induced thermal therapy.

Quantification of local variations in the optical properties of tumor tissue introduced by the presence of gold-silica nanoparticles (NP) presents significant opportunities in monitoring and control of NP-mediated laser induced thermal therapy (LITT) procedures. Finite element methods of inverse parameter recovery constrained by a Pennes bioheat transfer model were applied to estimate the optical parameters. Magnetic resonance temperature imaging (MRTI) acquired during a NP-mediated LITT of a canine transmissible venereal tumor in brain was used in the presented statistical inverse problem formulation. The maximum likelihood (ML) value of the optical parameters illustrated a marked change in the periphery of the tumor corresponding with the expected location of NP and area of selective heating observed on MRTI. Parameter recovery information became increasingly difficult to infer in distal regions of tissue where photon fluence had been significantly attenuated. Finite element temperature predictions using the ML parameter values obtained from the solution of the inverse problem are able to reproduce the NP selective heating within 5 °C of measured MRTI estimations along selected temperature profiles. Results indicate the ML solution found is able to sufficiently reproduce the selectivity of the NP mediated laser induced heating and therefore the ML solution is likely to return useful optical parameters within the region of significant laser fluence.

Kalman filtered MR temperature imaging for laser induced thermal therapies.

The feasibility of using a stochastic form of Pennes bioheat model within a 3-D finite element based Kalman filter (KF) algorithm is critically evaluated for the ability to provide temperature field estimates in the event of magnetic resonance temperature imaging (MRTI) data loss during laser induced thermal therapy (LITT). The ability to recover missing MRTI data was analyzed by systematically removing spatiotemporal information from a clinical MR-guided LITT procedure in human brain and comparing predictions in these regions to the original measurements. Performance was quantitatively evaluated in terms of a dimensionless L(2) (RMS) norm of the temperature error weighted by acquisition uncertainty. During periods of no data corruption, observed error histories demonstrate that the Kalman algorithm does not alter the high quality temperature measurement provided by MR thermal imaging. The KF-MRTI implementation considered is seen to predict the bioheat transfer with RMS error < 4 for a short period of time, ∆t < 10 s, until the data corruption subsides. In its present form, the KF-MRTI method currently fails to compensate for consecutive for consecutive time periods of data loss ∆t > 10 sec.

Adaptive real-time bioheat transfer models for computer-driven MR-guided laser induced thermal therapy.

The treatment times of laser induced thermal therapies (LITT) guided by computational prediction are determined by the convergence behavior of partial differential equation (PDE)-constrained optimization problems. In this paper, we investigate the convergence behavior of a bioheat transfer constrained calibration problem to assess the feasibility of applying to real-time patient specific data. The calibration techniques utilize multiplanar thermal images obtained from the nondestructive in vivo heating of canine prostate. The calibration techniques attempt to adaptively recover the biothermal heterogeneities within the tissue on a patient-specific level and results in a formidable PDE constrained optimization problem to be solved in real time. A comprehensive calibration study is performed with both homogeneous and spatially heterogeneous biothermal model parameters with and without constitutive nonlinearities. Initial results presented here indicate that the calibration problems involving the inverse solution of thousands of model parameters can converge to a solution within three minutes and decrease the [see text for symbol](L) (2) (2) ((0, T; L) (2) ((Omega))) norm of the difference between computational prediction and the measured temperature values to a patient-specific regime.

Computational modeling and real-time control of patient-specific laser treatment of cancer.

An adaptive feedback control system is presented which employs a computational model of bioheat transfer in living tissue to guide, in real-time, laser treatments of prostate cancer monitored by magnetic resonance thermal imaging. The system is built on what can be referred to as cyberinfrastructure-a complex structure of high-speed network, large-scale parallel computing devices, laser optics, imaging, visualizations, inverse-analysis algorithms, mesh generation, and control systems that guide laser therapy to optimally control the ablation of cancerous tissue. The computational system has been successfully tested on in vivo, canine prostate. Over the course of an 18 min laser-induced thermal therapy performed at M.D. Anderson Cancer Center (MDACC) in Houston, Texas, the computational models were calibrated to intra-operative real-time thermal imaging treatment data and the calibrated models controlled the bioheat transfer to within 5 degrees C of the predetermined treatment plan. The computational arena is in Austin, Texas and managed at the Institute for Computational Engineering and Sciences (ICES). The system is designed to control the bioheat transfer remotely while simultaneously providing real-time remote visualization of the on-going treatment. Post-operative histology of the canine prostate reveal that the damage region was within the targeted 1.2 cm diameter treatment objective.

Risk factors for infection with Campylobacter jejuni flaA genotypes.

We aimed to explore Campylobacter genotype-specific risk factors in Australia. Isolates collected prospectively from cases recruited into a case-control study were genotyped using flaA restriction fragment-length polymorphism typing (flaA genotyping). Exposure information for cases and controls was collected by telephone interview. Risk factors were examined for major flaA genotypes using logistic and multinomial regression. Five flaA genotypes accounted for 325 of 590 (55%) cases - flaA-6b (n=129), flaA-6 (n=70), flaA-10 (n=48), flaA-2 (n=43), flaA-131 (n=35). In Australia, infections due to flaA-10 and flaA-2 were found to be significantly associated with eating non-poultry meat (beef and ham, respectively) in both case-control and inter-genotype comparisons. All major genotypes apart from flaA-10 were associated with chicken consumption in the case-control comparisons. Based on several clinical criteria, infections due to flaA-2 were more severe than those due to other genotypes. Thus genotype analysis may reveal genotype-specific niches and differences in virulence and transmission routes.

A multi-centre prospective case-control study of campylobacter infection in persons aged 5 years and older in Australia.

There are an estimated 277,000 cases of campylobacteriosis in Australia each year, most of which are thought to be sporadically acquired. To explore causes for these infections, we conducted a multi-centre case-control study of patients and community controls across five Australian States during 2001-2002. A total of 881 campylobacter cases and 833 controls aged 5 years were recruited into the study. Crude logistic analyses were conducted within various food and non-food exposure groups. A final most parsimonious multivariable logistic regression model was developed and adjusted odds ratios (aOR), 95% confidence intervals (95% CI) were derived together with adjusted population attributable risks (PAR). Consumption of undercooked chicken (aOR 4.7, 95% CI 2.6-8.4) and offal (aOR 2.0, 95% CI 1.0-4.0), ownership of domestic chickens aged<6 months (aOR 12.4, 95% CI 2.6-59.3) and domestic dogs aged<6 months (aOR 2.1, 95% CI 1.1-4.2) were found to be independent risk factors for illness in the final model. The PAR proportions indicate that eating chicken meat, either cooked or undercooked may account for approximately 30% of campylobacter cases that occur each year in Australia. These results justify the continued need for education of consumers and foodhandlers about the risks associated with the handling of raw chicken and the potential for cross-contamination.

Risk factors for campylobacter infection in infants and young children: a matched case-control study.

Campylobacter infection has one of the highest rates of all the notifiable diseases in Australia, with a peak in children aged 0-35 months. A matched case-control study was conducted to investigate risk factors for campylobacter infection for children in this age group. Eighty-one cases and 144 controls were enrolled in the study that was conducted between 24 January 1996 and 21 January 1997. The following risk factors were found to be independently associated with illness: ownership of pet puppies (adjusted odds ratio [OR] 16.58, 95% confidence interval [CI] 3.73-73.65) and pet chickens (OR 11.80, CI 1.37-101.75), and consumption of mayonnaise (OR 4.13, CI 1.61-10.59). We propose that children aged less than 3 years are at risk of campylobacter infection if residing in a household which has puppies or chickens as pets.