Design and development of a novel flexible ultra-short echo time (FUSE) sequence.

PURPOSE: To present the validation of a new Flexible Ultra-Short Echo time (FUSE) pulse sequence using a short-T2 phantom. METHODS: FUSE was developed to include a range of RF excitation pulses, trajectories, dimensionalities, and long-T2 suppression techniques, enabling real-time interchangeability of acquisition parameters. Additionally, we developed an improved 3D deblurring algorithm to correct for off-resonance artifacts. Several experiments were conducted to validate the efficacy of FUSE, by comparing different approaches for off-resonance artifact correction, variations in RF pulse and trajectory combinations, and long-T2 suppression techniques. All scans were performed on a 3 T system using an in-house short-T2 phantom. The evaluation of results included qualitative comparisons and quantitative assessments of the SNR and contrast-to-noise ratio. RESULTS: Using the capabilities of FUSE, we demonstrated that we could combine a shorter readout duration with our improved deblurring algorithm to effectively reduce off-resonance artifacts. Among the different RF and trajectory combinations, the spiral trajectory with the regular half-inc pulse achieves the highest SNRs. The dual-echo subtraction technique delivers better short-T2 contrast and superior suppression of water and agar signals, whereas the off-resonance saturation method successfully suppresses water and lipid signals simultaneously. CONCLUSION: In this work, we have validated the use of our new FUSE sequence using a short T2 phantom, demonstrating that multiple UTE acquisitions can be achieved within a single sequence. This new sequence may be useful for acquiring improved UTE images and the development of UTE imaging protocols.

Feasibility study for marker-based VMAT plan optimization toward tumor tracking.

This work investigates the incorporation of fiducial marker-based visibility parameters into the optimization of volumetric modulated arc therapy (VMAT) plans. We propose that via this incorporation, one may produce treatment plans that aid real-time tumor tracking approaches employing exit imaging of the therapeutic beam (e.g., via EPID), in addition to satisfying purely dosimetric requirements. We investigated the feasibility of this approach for a thorax and prostate site using optimization software (MonArc). For a thorax phantom and a lung patient, three fiducial markers were inserted around the tumor and VMAT plans were created with two partial arcs and prescription dose of 48 Gy (4 fractions). For a prostate patient with three markers in the prostate organ, a VMAT plan was created with two partial arcs and prescription dose 72.8 Gy (28 fractions). We modified MonArc to include marker-based visibility constraints ("hard"and "soft"). A hard constraint (HC) imposes full visibility for all markers, while a soft constraint (SC) penalizes visibility for specific markers in the beams-eye-view. Dose distributions from constrained plans (HC and SC) were compared to the reference nonconstrained (NC) plan using metrics including conformity index (CI), homogeneity index (HI), gradient measure (GM), and dose to 95% of planning target volume (PTV) and organs at risk (OARs). The NC plan produced the best target conformity and the least doses to the OARs for the entire dataset, followed by the SC and HC plans. Using SC plans provided acceptable dosimetric tolerances for both the target and OARs. However, OAR doses may be increased or decreased based on the constrained marker location and number of trackable markers. In conclusion, we demonstrate that visibility constraints can be incorporated into the optimization together with dosimetric objectives to produce treatment plans satisfying both objectives. This approach should ensure greater clinical success when applying real-time tracking algorithms, using VMAT delivery.

Trends in targeted prostate brachytherapy: from multiparametric MRI to nanomolecular radiosensitizers.

The treatment of localized prostate cancer is expected to become a significant problem in the next decade as an increasingly aging population becomes prone to developing the disease. Recent research into the biological nature of prostate cancer has shown that large localized doses of radiation to the cancer offer excellent long-term disease control. Brachytherapy, a form of localized radiation therapy, has been shown to be one of the most effective methods for delivering high radiation doses to the cancer; however, recent evidence suggests that increasing the localized radiation dose without bound may cause unacceptable increases in long-term side effects. This review focuses on methods that have been proposed, or are already in clinical use, to safely escalate the dose of radiation within the prostate. The advent of multiparametric magnetic resonance imaging (mpMRI) to better identify and localize intraprostatic tumors, and nanomolecular radiosensitizers such as gold nanoparticles (GNPs), may be used synergistically to increase doses to cancerous tissue without the requisite hazard of increased side effects.

A clinically relevant method to screen for hepatic steatosis in overweight adolescents: a cross sectional study.

BACKGROUND: To develop a screening algorithm to detect hepatic steatosis in overweight and obese adolescents. METHODS: We performed a cross sectional study of 129 overweight adolescents 13-18 yrs. The primary outcome, hepatic steatosis was defined as an intracellular triglyceride content > 5.5 mg/g and quantified using (1)H-magenetic resonance spectroscopy. Primary predictor variables included, alanine and aspartate transaminases (ALT/AST) and features of the metabolic syndrome. RESULTS: Hepatic steatosis was present in 33% of overweight and obese adolescents. Adolescents with hepatic steatosis were more likely to be boys (adjusted OR: 4.8; 95% CI: 2.5-10.5), display a higher waist circumference (111 ± 12 vs 100 ± 13 cm, p < 0.001) and have metabolic syndrome (adjusted OR: 5.1; 95% CI: 1.6-16.4). Serum ALT predicted hepatic steatosis in boys (AUC: 0.82; 95% CI: 0.70-0.95; p < 0.001) but not girls (AUC = 0.63; 95% CI: 0.46-0.75, p = 0.16). An ALT >20 U/L, combined with the presence of metabolic syndrome, male gender and an elevated waist circumference provided the best model (AUC 0.85) with high sensitivity (72%) and specificity (82%) and positive and negative predictive values of 61% and 89% respectively. CONCLUSIONS: Serum transaminases provide modest predictive value for hepatic steatosis in youth. The ALT threshold for predicting hepatic steatosis is significantly lower than current clinical thresholds for predicting non-alcoholic fatty liver disease. The addition of ALT, presence of the metabolic syndrome and male gender significant improve the ability to predict hepatic steatosis.

Pancreatic lipid content is not associated with beta cell dysfunction in youth-onset type 2 diabetes.

OBJECTIVE: To determine whether pancreatic lipid content is associated with type 2 diabetes and beta cell function in Indigenous and Caucasian adolescents. METHODS: This was a cross-sectional study comparing (1)H-magnetic resonance spectroscopy-derived pancreatic triglyceride content in adolescents 13 to 18 years of age with type 2 diabetes (n=20) and body mass index-matched normoglycemic controls (n=34). Beta cell function was measured by the acute insulin response and disposition index derived from intravenous glucose tolerance tests. RESULTS: Pancreatic lipid content was not significantly different in youth with type 2 diabetes and their normoglycemic body mass index-matched peers (2.41 [95% CI: 0.63, 5.60] vs. 1.22 [0.08, 5.93]; p=0.27). Pancreatic triglyceride levels were not associated with measures of beta cell function in the cohort. In subgroup analyses, pancreatic lipid content was ∼4-fold higher in youth with type 2 diabetes who were carriers of the G319S mutation in the HNF-1alpha gene (7.45 [2.85, 26.8] vs. 2.20 [0.350, 3.30] % Fat to Water Ratio F/W; p=0.032). CONCLUSIONS: Pancreatic lipid content is not elevated in Indigenous or Caucasian youth with type 2 diabetes compared to normoglycemic youth, nor is it associated with beta cell function. The presence of the G319S mutation in the HNF-1alpha gene in Indigenous youth with type 2 diabetes is associated with higher pancreatic lipid content. Further research is needed to understand the mechanisms that explain beta cell failure in overweight youth with type 2 diabetes.

Electromagnetic tracking for catheter reconstruction in ultrasound-guided high-dose-rate brachytherapy of the prostate.

PURPOSE: The accurate delivery of high-dose-rate brachytherapy is dependent on the correct identification of the position and shape of the treatment catheters. In many brachytherapy clinics, transrectal ultrasound (TRUS) imaging is used to identify the catheters. However, manual catheter identification on TRUS images can be time consuming, subjective, and operator dependent because of calcifications and distal shadowing artifacts. We report the use of electromagnetic (EM) tracking technology to map the position and shape of catheters inserted in a tissue-mimicking phantom. METHODS AND MATERIALS: The accuracy of the EM system was comprehensively quantified using a three-axis robotic system. In addition, EM tracks acquired from catheters in a phantom were compared with catheter positions determined from TRUS and CT images to compare EM system performance to standard clinical imaging modalities. The tracking experiments were performed in a controlled laboratory environment and also in a typical brachytherapy operating room to test for potential EM distortions. RESULTS: The robotic validation of the EM system yielded a mean accuracy of <0.5 mm for a clinically acceptable field of view in a nondistorting environment. The EM-tracked catheter representations were found to have an accuracy of <1 mm when compared with TRUS- and CT-identified positions, both in the laboratory environment and in the brachytherapy operating room. The achievable accuracy depends to a large extent on the calibration of the TRUS probe, geometry of the tracked devices relative to the EM field generator, and locations of surrounding clinical equipment. To address the issue of variable accuracy, a robust calibration algorithm has been developed and integrated into the workflow. The proposed mapping technique was also found to improve the workflow efficiency of catheter identification. CONCLUSIONS: The high baseline accuracy of the EM system, the consistent agreement between EM-tracked, TRUS- and CT-identified catheters, and the improved workflow efficiency illustrate the potential value of using EM tracking for catheter mapping in high-dose-rate brachytherapy.

Cardiorespiratory fitness and adiposity in metabolically healthy overweight and obese youth.

OBJECTIVE: Controversy exists surrounding the contribution of fitness and adiposity as determinants of the Metabolically Healthy Overweight(MHO) phenotype in youth. This study investigated the independent contribution of cardiorespiratory fitness and adiposity to the MHO phenotype among overweight and obese youth. METHODS: This cross-sectional study included 108 overweight and obese youth classified as MHO (no cardiometabolic risk factors) or non-MHO (≥1 cardiometabolic risk factor), based on age- and gender specific cut-points for fasting glucose, triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and hepaticsteatosis. RESULTS: Twenty-five percent of overweight and obese youth were classified as MHO. This phenotype was associated with lower BMIz-score (BMI z-score: 1.8 ± 0.3 vs 2.1 ± 0.4, P = .02) and waist circumference (99.7 ± 13.2 vs 106.1 ± 13.7 cm, P = .04) compared with non-MHO youth. When matched for fitness level and stratified by BMI z-score (1.6 ± 0.3 vs 2.4 ± 0.2), the prevalence of MHO was four fold higher in the low BMI z-score group (27% vs 7%; P = .03).Multiple logistic regression analyses revealed that the best predictor of MHO was the absence of hepatic steatosis even after adjusting for waist circumference (odds ratio 0.57, 95% confidence interval 0.40­0.80) or BMI z-score (odds ratio 0.59, 95% confidence interval 0.43­0.80). CONCLUSIONS: The MHO phenotype was present in 25% of overweight and obese youth and is strongly associated with lower levels of adiposity,and the absence of hepatic steatosis, but not with cardiorespiratory fitness.

Short echo time in vivo prostate ¹H-MRSI.

Visualization of short echo time (TE) metabolites in prostate magnetic resonance spectroscopic imaging is difficult due to lipid contamination and pulse timing constraints. In this work, we present a modified pulse sequence to permit short echo time (TE=40ms) acquisitions with reduced lipid contamination for the detection of short TE metabolites. The modified pulse sequence employs the conformal voxel MRS (CV-MRS) technique, which automatically optimizes the placement of spatial saturation planes to adapt the excitation volume to the shape of the prostate, thus reducing lipid contamination in prostate magnetic resonance spectroscopic imaging (MRSI). Metabolites were measured and assessed using a modified version of LCModel for analysis of in vivo prostate spectra. We demonstrate the feasibility of acquiring high quality spectra at short TEs, and show the measurement of short TE metabolites, myo-inositol, scyllo-inositol, taurine and glutamine/glutamate for both single and multi-voxel acquisitions. In single voxels experiments, the reduction in TE resulted in 57% improvement in the signal-to-noise ratio (SNR). Additional 3D MRSI experiments comparing short (TE=40 ms), and long (TE=130 ms) TE acquisitions revealed a 35% improvement in the number of adequately fitted metabolite peaks (775 voxels over all subjects). This resulted in a 42 ± 24% relative improvement in the number of voxels with detectable citrate that were well-fitted using LCmodel. In this study, we demonstrate that high quality prostate spectra can be obtained by reducing the TE to 40 ms to detect short T2 metabolites, while maintaining positive signal intensity of the spin-coupled citrate multiplet and managing lipid suppression.

Real time MRI prostate segmentation based on wavelet multiscale products flow tracking.

Currently, prostate cancer is the third leading cause of cancer-related deaths among men in North America. As with many others types of cancer, early detection and treatment greatly increases the patient's chance of survival. Combined Magnetic Resonance Imaging and Spectroscopic Imaging (MRI/MRSI) techniques have became a reliable tool for early stage prostate cancer detection. Nevertheless, their performance is strongly affected by the determination of the region of interest (ROI) prior to data acquisition process. The process of executing prostate MRI/MRSI techniques can be significantly enhanced by segmenting the whole prostate. A novel method for segmentation of the prostate in MRI datasets is presented. This method exploits the different behavior presented by signal singularities and noise in the wavelet domain in order to accurately detect the borders around the prostate. The prostate contour is then traced by using a set of spatially variant rules that are based on prior knowledge about the general shape of the prostate. The proposed method yielded promising results when applied to clinical datasets.

Semi automatic MRI prostate segmentation based on wavelet multiscale products.

Currently, prostate cancer is the third leading cause of cancer-related deaths among men in North America. As with many others types of cancer, early detection and treatment greatly increases the patient's chance of survival. MRI prostate segmentation allows clinical personnel to design an accurate treatment plan. A novel method for MRI prostate imagery segmentation is proposed in this paper. This method exploits the different behavior presented by signal singularities and noise in the wavelet domain in order to accurately detect the borders around the prostate. The prostate contour is then traced by using a set of spatially variant rules that are based on prior knowledge about the general shape of the prostate. The proposed method yielded promising results when applied to real data.

A feasibility study to investigate the use of thin-plate splines to account for prostate deformation.

Image registration is an important step in the radiotherapy treatment planning process. It provides a method of fusing different types of diagnostic imaging information. One such application is to combine magnetic resonance spectroscopic images (MRSI) of the prostate with anatomical MRI and/or computed tomography images that are routinely used in the radiation treatment planning of prostate cancer. MRSI provides in vivo information related to the underlying metabolic activity of tissues, and can be related to the presence of cancer. However, the inflated endorectal coil required during MRS imaging poses a potential problem by deforming the prostate when it is filled with approximately 100 cm3 of air during image acquisition. This pushes the prostate superiorly/anteriorly, deforming the prostate and consequently the spectroscopic imaging data in a nonlinear manner. In this application, the coil-deformed MRS images are warped back to a non-deformed state, using a single data set. A nonlinear warping algorithm is presented to achieve this. Results indicate that the algorithm attains an accuracy of 97% (4 cm3 difference) when reproducing the total prostate volume compared to a Radiation Oncologist defined prostate volume. This difference is slightly smaller than the measured intra-operator variance of +/-1.5 cm3 (deflated coil) and the measured algorithm variance of +/-1.0 cm3. Additionally, intraprostatic nodules were used to assess the accuracy of the warping algorithm in regions inside the prostate. While choosing anatomical tie points along the external prostate surface, analysis of the nodules revealed the algorithm accuracy reduced to 63-93%.