Towards a universal MRI atlas of the prostate and prostate zones : Comparison of MRI vendor and image acquisition parameters.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate an automatic multi-atlas-based segmentation method for generating prostate, peripheral (PZ), and transition zone (TZ) contours on MRIs with and without fat saturation (±FS), and compare MRIs from different vendor MRI systems. METHODS: T2-weighted (T2) and fat-saturated (T2FS) MRIs were acquired on 3T GE (GE, Waukesha, WI, USA) and Siemens (Erlangen, Germany) systems. Manual prostate and PZ contours were used to create atlas libraries. As a test MRI is entered, the procedure for atlas segmentation automatically identifies the atlas subjects that best match the test subject, followed by a normalized intensity-based free-form deformable registration. The contours are transformed to the test subject, and Dice similarity coefficients (DSC) and Hausdorff distances between atlas-generated and manual contours were used to assess performance. RESULTS: Three atlases were generated based on GE_T2 (n = 30), GE_T2FS (n = 30), and Siem_T2FS (n = 31). When test images matched the contrast and vendor of the atlas, DSCs of 0.81 and 0.83 for T2 ± FS were obtained (baseline performance). Atlases performed with higher accuracy when segmenting (i) T2FS vs. T2 images, likely due to a superior contrast between prostate vs. surrounding tissue; (ii) prostate vs. zonal anatomy; (iii) in the mid-gland vs. base and apex. Atlases performance declined when tested with images with differing contrast and MRI vendor. Conversely, combined atlases showed similar performance to baseline. CONCLUSION: The MRI atlas-based segmentation method achieved good results for prostate, PZ, and TZ compared to expert contoured volumes. Combined atlases performed similarly to matching atlas and scan type. The technique is fast, fully automatic, and implemented on commercially available clinical platform.

Validation of a deformable MRI to CT registration algorithm employing same day planning MRI for surrogate analysis.

PURPOSE: Validating deformable multimodality image registrations is challenging due to intrinsic differences in signal characteristics and their spatial intensity distributions. Evaluating multimodality registrations using these spatial intensity distributions is also complicated by the fact that these metrics are often employed in the registration optimization process. This work evaluates rigid and deformable image registrations of the prostate in between diagnostic-MRI and radiation treatment planning-CT by utilizing a planning-MRI after fiducial marker placement as a surrogate. The surrogate allows for the direct quantitative analysis that can be difficult in the multimodality domain. METHODS: For thirteen prostate patients, T2 images were acquired at two different time points, the first several weeks prior to planning (diagnostic-MRI) and the second on the same day as the planning-CT (planning-MRI). The diagnostic-MRI was deformed to the planning-CT utilizing a commercially available algorithm which synthesizes a deformable image registration (DIR) algorithm from local rigid registrations. The planning-MRI provided an independent surrogate for the planning-CT for assessing registration accuracy using image similarity metrics, including Pearson correlation and normalized mutual information (NMI). A local analysis was performed by looking only within the prostate, proximal seminal vesicles, penile bulb, and combined areas. RESULTS: The planning-MRI provided an excellent surrogate for the planning-CT with residual error in fiducial alignment between the two datasets being submillimeter, 0.78 mm. DIR was superior to the rigid registration in 11 of 13 cases demonstrating a 27.37% improvement in NMI (P < 0.009) within a regional area surrounding the prostate and associated critical organs. Pearson correlations showed similar results, demonstrating a 13.02% improvement (P < 0.013). CONCLUSION: By utilizing the planning-MRI as a surrogate for the planning-CT, an independent evaluation of registration accuracy is possible. This population provides an ideal testing ground for MRI to CT DIR by obviating the need for multimodality comparisons which are inherently more challenging.

Dynamic contrast-enhanced MRI for automatic detection of foci of residual or recurrent disease after prostatectomy.

PURPOSE: This study aimed to develop an automated procedure for identifying suspicious foci of residual/recurrent disease in the prostate bed using dynamic contrast-enhanced-MRI (DCE-MRI) in prostate cancer patients after prostatectomy. MATERIALS AND METHODS: Data of 22 patients presenting for salvage radiotherapy (RT) with an identified gross tumor volume (GTV) in the prostate bed were analyzed retrospectively. An unsupervised pattern recognition method was used to analyze DCE-MRI curves from the prostate bed. Data were represented as a product of a number of signal-vs.-time patterns and their weights. The temporal pattern, characterized by fast wash-in and gradual wash-out, was considered the "tumor" pattern. The corresponding weights were thresholded based on the number (1, 1.5, 2, 2.5) of standard deviations away from the mean, denoted as DCE1.0, …, DCE2.5, and displayed on the T2-weighted MRI. The resultant four volumes were compared with the GTV and maximum pre-RT prostate-specific antigen (PSA) level. Pharmacokinetic modeling was also carried out. RESULTS: Principal component analysis determined 2-4 significant patterns in patients' DCE-MRI. Analysis and display of the identified suspicious foci was performed in commercial software (MIM Corporation, Cleveland, OH, USA). In general, DCE1.0/DCE1.5 highlighted larger areas than GTV. DCE2.0 and GTV were significantly correlated (r = 0.60, p < 0.05). DCE2.0/DCA2.5 were also significantly correlated with PSA (r = 0.52, 0.67, p < 0.05). Ktrans for DCE2.5 was statistically higher than the GTV's Ktrans (p < 0.05), indicating that the automatic volume better captures areas of malignancy. CONCLUSION: A software tool was developed for identification and visualization of the suspicious foci in DCE-MRI from post-prostatectomy patients and was integrated into the treatment planning system.

A review of nonstandardized applicators digitization in Nucletron™ HDR procedures.

The major errors in HDR procedures were failures to enter the correct treatment distance, which could be caused by either entering wrong transmission lengths or imprecisely digitizing the dwelling positions. Most of those errors were not easily avoidable by enhancing the HDR management level because they were caused by implementations of nonstandardized applicators utilizing transmission tubes of different lengths in standard HDR procedures. We performed this comprehensive study to include all possible situations with different nonstandardized applicators that frequently occurred in HDR procedures, provide corresponding situations with standard applicator as comparisons, list all possible errors and in planning, clarify the confusions in offsets setting, and provide mathematical and quantitative solutions for each given scenarios. Training on HDR procedures with nonstandardized applicators are normally not included in most residential program for medical physics, thus this study could be meaningful in both clinical and educational purpose. At precision of 1 mm, our study could be used as the essential and practical reference for finding the correct treatment length as well as locating the accurate dwelling positions in any HDR procedure with nonstandardized applicators.

Evaluation of the tool "Reg Refine" for user-guided deformable image registration.

"Reg Refine" is a tool available in the MIM Maestro v6.4.5 platform (www.mim-software.com) that allows the user to actively participate in the deformable image registration process. The purpose of this work was to evaluate the efficacy of this tool and investigate strategies for how to apply it effectively. This was done by performing DIR on two publicly available ground-truth models, the Pixel-based Breathing Thorax Model (POPI) for lung, and the Deformable Image Registration Evaluation Project (DIREP) for head and neck. Image noise matched in both magnitude and texture to clinical CBCT scans was also added to each model to simulate the use case of CBCT-CT alignment. For lung, the results showed Reg Refine effective at improving registration accuracy when controlled by an expert user within the context of large lung deformation. CBCT noise was also shown to have no effect on DIR performance while using the MIM algorithm for this site. For head and neck, the results showed CBCT noise to have a large effect on the accuracy of registration, specifically for low-contrast structures such as the brain-stem and parotid glands. In these cases, the Reg Refine tool was able to improve the registration accuracy when controlled by an expert user. Several strategies for how to achieve these results have been outlined to assist other users and provide feedback for developers of similar tools.

A defect in the mitochondrial complex III, but not complex IV, triggers early ROS-dependent damage in defined brain regions.

We have created two neuron-specific mouse models of mitochondrial electron transport chain deficiencies involving defects in complex III (CIII) or complex IV (CIV). These conditional knockouts (cKOs) were created by ablation of the genes coding for the Rieske iron-sulfur protein (RISP) and COX10, respectively. RISP is one of the catalytic subunits of CIII and COX10 is an assembly factor indispensable for the maturation of Cox1, one of the catalytic subunits of CIV. Although the rates of gene deletion, protein loss and complex dysfunction were similar, the RISP cKO survived 3.5 months of age, whereas the COX10 cKO survived for 10-12 months. The RISP cKO had a sudden death, with minimal behavioral changes. In contrast, the COX10 cKO showed a distinctive behavioral phenotype with onset at 4 months of age followed by a slower but progressive neurodegeneration. Curiously, the piriform and somatosensory cortices were more vulnerable to the CIII defect whereas cingulate cortex and to a less extent piriform cortex were affected preferentially by the CIV defect. In addition, the CIII model showed severe and early reactive oxygen species damage, a feature not observed until very late in the pathology of the CIV model. These findings illustrate how specific respiratory chain defects have distinct molecular mechanisms, leading to distinct pathologies, akin to the clinical heterogeneity observed in patients with mitochondrial diseases.

Cone beam CT-based adaptive intensity modulated proton therapy assessment using automated planning for head-and-neck cancer.

BACKGROUND: To assess the feasibility of CBCT-based adaptive intensity modulated proton therapy (IMPT) using automated planning for treatment of head and neck (HN) cancers. METHODS: Twenty HN cancer patients who received radiotherapy and had pretreatment CBCTs were included in this study. Initial IMPT plans were created using automated planning software for all patients. Synthetic CTs (sCT) were then created by deforming the planning CT (pCT) to the pretreatment CBCTs. To assess dose calculation accuracy on sCTs, repeat CTs (rCTs) were deformed to the pretreatment CBCT obtained on the same day to create deformed rCT (rCTdef), serving as gold standard. The dose recalculated on sCT and on rCTdef were compared by using Gamma analysis. The accuracy of DIR generated contours was also assessed. To explore the potential benefits of adaptive IMPT, two sets of plans were created for each patient, a non-adapted IMPT plan and an adapted IMPT plan calculated on weekly sCT images. The weekly doses for non-adaptive and adaptive IMPT plans were accumulated on the pCT, and the accumulated dosimetric parameters of two sets were compared. RESULTS: Gamma analysis of the dose recalculated on sCT and rCTdef resulted in a passing rate of 97.9% ± 1.7% using 3 mm/3% criteria. With the physician-corrected contours on the sCT, the dose deviation range of using sCT to estimate mean dose for the most organ at risk (OARs) can be reduced to (- 2.37%, 2.19%) as compared to rCTdef, while for V95 of primary or secondary CTVs, the deviation can be controlled within (- 1.09%, 0.29%). Comparison of the accumulated doses from the adaptive planning against the non-adaptive plans reduced mean dose to constrictors (- 1.42 Gy ± 2.79 Gy) and larynx (- 2.58 Gy ± 3.09 Gy). The reductions result in statistically significant reductions in the normal tissue complication probability (NTCP) of larynx edema by 7.52% ± 13.59%. 4.5% of primary CTVs, 4.1% of secondary CTVs, and 26.8% tertiary CTVs didn't meet the V95 > 95% constraint on non-adapted IMPT plans. All adaptive plans were able to meet the coverage constraint. CONCLUSION: sCTs can be a useful tool for accurate proton dose calculation. Adaptive IMPT resulted in better CTV coverage, OAR sparing and lower NTCP for some OARs as compared with non-adaptive IMPT.

Increasing the efficiency of cone-beam CT based delta-radiomics using automated contours to predict radiotherapy-related toxicities in prostate cancer.

Extracting longitudinal image quantitative data, known as delta-radiomics, has the potential to capture changes in a patient's anatomy throughout the course of radiation treatment for prostate cancer. Some of the major challenges of delta-radiomics studies are contouring the structures for individual fractions and accruing patients' data in an efficient manner. The manual contouring process is often time consuming and would limit the efficiency of accruing larger sample sizes for future studies. The problem is amplified because the contours are often made by highly trained radiation oncologists with limited time to dedicate to research studies of this nature. This work compares the use of automated prostate contours generated using a deformable image-based algorithm to make predictive models of genitourinary and changes in total international prostate symptom score in comparison to manually contours for a cohort of fifty patients. Area under the curve of manual and automated models were compared using the Delong test. This study demonstrated that the delta-radiomics models were similar for both automated and manual delta-radiomics models.

Stereotactic MR-guided on-table adaptive radiation therapy (SMART) for borderline resectable and locally advanced pancreatic cancer: A multi-center, open-label phase 2 study.

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity. MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 patients (LAPC 56.6 %; BRPC 43.4 %) after ≥ 3 months of any chemotherapy without distant progression and CA19-9 ≤ 500 U/mL. SMART was delivered on a 0.35 T MR-guided system prescribed to 50 Gy in 5 fractions (biologically effective dose10 [BED10] = 100 Gy). Elective coverage was optional. Surgery and chemotherapy were permitted after SMART. RESULTS: Mean age was 65.7 years (range, 36-85), induction FOLFIRINOX was common (81.7 %), most received elective coverage (57.4 %), and 34.6 % had surgery after SMART. Median FU was 22.9 months from diagnosis and 14.2 months from SMART, respectively. 2-year OS from diagnosis and SMART were 53.6 % and 40.5 %, respectively. Late grade ≥ 3 toxicity definitely, probably, or possibly attributed to SMART were observed in 0 %, 4.6 %, and 11.5 % patients, respectively. CONCLUSIONS: Long-term outcomes from the phase 2 SMART trial demonstrate encouraging OS and limited severe toxicity. Additional prospective evaluation of this novel strategy is warranted.

Monitoring steady flow effects on cell distribution in engineered valve tissues by magnetic resonance imaging.

In heart valve tissue engineering, assessment of cell migration under dynamic states can provide insights on the evolving tissue structure. We labeled human vascular smooth muscle (SMCs), endothelial (ECs), and bone marrow-derived mesenchymal stem cells (BMSCs) with superparamagnetic iron oxide (SPIO) microparticles and visualized them using magnetic resonance imaging (MRI) under steady flow. We determined that vascular cells were able to remain reasonably viable and proliferate well after being labeled with SPIO microparticles (200 µg/mL) for 48 hours. SPIO-labeled cells were successfully visualized using T2* contrast. When physiologically representative shear stresses (5-6 dynes/cm2) were applied to SMC-EC coculture-seeded scaffolds, hypointense regions seemed to have decreased after 2 weeks in some locations, whereas others revealed sustained levels of T2* contrast; similar observations were seen in the case of BMSC-seeded scaffolds. This could be attributable to increased out-of-plane cell migratory activity, which occurred from the fluid-induced mechanical cues received, which was not previously evidenced in static culture. Vascular cells and BMSCs were labeled with remarkably high concentrations of SPIO. Moreover, steady fluid flow enhanced intrascaffold cell migration of vascular SMCs and ECs as well as BMSCs, which, in turn, significantly improved construct cellularity and extracellular collagen content.

Multimodal magnetic resonance imaging after experimental moderate and severe traumatic brain injury: A longitudinal correlative assessment of structural and cerebral blood flow changes.

Traumatic brain injury (TBI) is a worldwide problem that results in death or disability for millions of people every year. Progressive neurological complications and long-term impairment can significantly disrupt quality of life. We demonstrated the feasibility of multiple magnetic resonance imaging (MRI) modalities to investigate and predict aberrant changes and progressive atrophy of gray and white matter tissue at several acute and chronic time points after moderate and severe parasagittal fluid percussion TBI. T2-weighted imaging, diffusion tensor imaging (DTI), and perfusion weighted imaging (PWI) were performed. Adult Sprague-Dawley rats were imaged sequentially on days 3, 14, and 1, 4, 6, 8, and 12 months following surgery. TBI caused dynamic white and gray matter alterations with significant differences in DTI values and injury-induced alterations in cerebral blood flow (CBF) as measured by PWI. Regional abnormalities after TBI were observed in T2-weighted images that showed hyperintense cortical lesions and significant cerebral atrophy in these hyperintense areas 1 year after TBI. Temporal DTI values indicated significant injury-induced changes in anisotropy in major white matter tracts, the corpus callosum and external capsule, and in gray matter, the hippocampus and cortex, at both early and chronic time points. These alterations were primarily injury-severity dependent with severe TBI exhibiting a greater degree of change relative to uninjured controls. PWI evaluating CBF revealed sustained global reductions in the cortex and in the hippocampus at most time points in an injury-independent manner. We next sought to investigate prognostic correlations across MRI metrics, timepoints, and cerebral pathology, and found that diffusion abnormalities and reductions in CBF significantly correlated with specific vulnerable structures at multiple time points, as well as with the degree of cerebral atrophy observed 1 year after TBI. This study further supports using DTI and PWI as a means of prognostic imaging for progressive structural changes after TBI and emphasizes the progressive nature of TBI damage.

AAPM Task Group Report 307: Use of EPIDs for Patient-Specific IMRT and VMAT QA.

PURPOSE: Electronic portal imaging devices (EPIDs) have been widely utilized for patient-specific quality assurance (PSQA) and their use for transit dosimetry applications is emerging. Yet there are no specific guidelines on the potential uses, limitations, and correct utilization of EPIDs for these purposes. The American Association of Physicists in Medicine (AAPM) Task Group 307 (TG-307) provides a comprehensive review of the physics, modeling, algorithms and clinical experience with EPID-based pre-treatment and transit dosimetry techniques. This review also includes the limitations and challenges in the clinical implementation of EPIDs, including recommendations for commissioning, calibration and validation, routine QA, tolerance levels for gamma analysis and risk-based analysis. METHODS: Characteristics of the currently available EPID systems and EPID-based PSQA techniques are reviewed. The details of the physics, modeling, and algorithms for both pre-treatment and transit dosimetry methods are discussed, including clinical experience with different EPID dosimetry systems. Commissioning, calibration, and validation, tolerance levels and recommended tests, are reviewed, and analyzed. Risk-based analysis for EPID dosimetry is also addressed. RESULTS: Clinical experience, commissioning methods and tolerances for EPID-based PSQA system are described for pre-treatment and transit dosimetry applications. The sensitivity, specificity, and clinical results for EPID dosimetry techniques are presented as well as examples of patient-related and machine-related error detection by these dosimetry solutions. Limitations and challenges in clinical implementation of EPIDs for dosimetric purposes are discussed and acceptance and rejection criteria are outlined. Potential causes of and evaluations of pre-treatment and transit dosimetry failures are discussed. Guidelines and recommendations developed in this report are based on the extensive published data on EPID QA along with the clinical experience of the TG-307 members. CONCLUSION: TG-307 focused on the commercially available EPID-based dosimetric tools and provides guidance for medical physicists in the clinical implementation of EPID-based patient-specific pre-treatment and transit dosimetry QA solutions including intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) treatments.

Single Fraction and Hypofractionated Radiation Cause Cochlear Damage, Hearing Loss, and Reduced Viability of Merlin-Deficient Schwann Cells.

BACKGROUND: Vestibular schwannomas (VS) are benign intracranial tumors caused by loss of function of the merlin tumor suppressor. We tested three hypotheses related to radiation, hearing loss (HL), and VS cell survival: (1) radiation causes HL by injuring auditory hair cells (AHC), (2) fractionation reduces radiation-induced HL, and (3) single fraction and equivalent appropriately dosed multi-fractions are equally effective at controlling VS growth. We investigated the effects of single fraction and hypofractionated radiation on hearing thresholds in rats, cell death pathways in rat cochleae, and viability of human merlin-deficient Schwann cells (MD-SC). METHODS: Adult rats received cochlear irradiation with single fraction (0 to 18 Gray [Gy]) or hypofractionated radiation. Auditory brainstem response (ABR) testing was performed for 24 weeks. AHC viabilities were determined using immunohistochemistry. Neonatal rat cochleae were harvested after irradiation, and gene- and cell-based assays were conducted. MD-SCs were irradiated, and viability assays and immunofluorescence for DNA damage and cell cycle markers were performed. RESULTS: Radiation caused dose-dependent and progressive HL in rats and AHC losses by promoting expression of apoptosis-associated genes and proteins. When compared to 12 Gy single fraction, hypofractionation caused smaller ABR threshold and pure tone average shifts and was more effective at reducing MD-SC viability. CONCLUSIONS: Investigations into the mechanisms of radiation ototoxicity and VS radiobiology will help determine optimal radiation regimens and identify potential therapies to mitigate radiation-induced HL and improve VS tumor control.

A Multi-Institutional Phase 2 Trial of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer.

PURPOSE: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). METHODS AND MATERIALS: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART. RESULTS: One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%. CONCLUSIONS: The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy.

Investigation of nanoparticles using magnetic resonance imaging after intravitreal injection.

BACKGROUND: Magnetic nanoparticles may be used for focal delivery for cells, plasmids or drugs, and other applications. Here we asked whether magnetic nanoparticles could be detected in vivo at different time points after intravitreal injection by magnetic resonance imaging. METHODS: Adult Sprague-Dawley rats received intravitreal injections of 50-nm or 4-µm magnetic particles into the left eye, with an equal volume of phosphate-buffered saline into the right eye (as controls). Animals were examined by magnetic resonance imaging at 1 h, 1 day and 5 weeks after injection. Eyes, brain, liver, spleen and kidney were also imaged with high-resolution ex vivo magnetic resonance imaging scanning. RESULTS: In vivo magnetic resonance imaging at the 1 h and 1 day time points more clearly detected magnetic particles in the 4 µm group compared with the 50-nm group, although 50-nm magnetic nanoparticles were easily visualized with high-resolution magnetic resonance imaging ex vivo. Five weeks after intravitreal injection magnetic resonance imaging clearly detected 4-µm particles inside the eye, but by this time point the 50-nm magnetic nanoparticles could not be detected by either in vivo or ex vivo high-resolution magnetic resonance imaging. No magnetic particles were detected in any other organ. CONCLUSIONS: Magnetic resonance imaging could be used to track magnetic nanoparticles in the eye with the dosing selected for this study. Clearance varies by size, with 50-nm magnetic nanoparticles cleared more quickly than 4-µm particles. Thus, nanoparticles may provide advantages over micron-scale particles when considering risks associated with long-term persistence.

Multi-parametric MRI (mpMRI) for treatment response assessment of radiation therapy.

Magnetic resonance imaging (MRI) plays an important role in the modern radiation therapy (RT) workflow. In comparison with computed tomography (CT) imaging, which is the dominant imaging modality in RT, MRI possesses excellent soft-tissue contrast for radiographic evaluation. Based on quantitative models, MRI can be used to assess tissue functional and physiological information. With the developments of scanner design, acquisition strategy, advanced data analysis, and modeling, multiparametric MRI (mpMRI), a combination of morphologic and functional imaging modalities, has been increasingly adopted for disease detection, localization, and characterization. Integration of mpMRI techniques into RT enriches the opportunities to individualize RT. In particular, RT response assessment using mpMRI allows for accurate characterization of both tissue anatomical and biochemical changes to support decision-making in monotherapy of radiation treatment and/or systematic cancer management. In recent years, accumulating evidence have, indeed, demonstrated the potentials of mpMRI in RT response assessment regarding patient stratification, trial benchmarking, early treatment intervention, and outcome modeling. Clinical application of mpMRI for treatment response assessment in routine radiation oncology workflow, however, is more complex than implementing an additional imaging protocol; mpMRI requires additional focus on optimal study design, practice standardization, and unified statistical reporting strategy to realize its full potential in the context of RT. In this article, the mpMRI theories, including image mechanism, protocol design, and data analysis, will be reviewed with a focus on the radiation oncology field. Representative works will be discussed to demonstrate how mpMRI can be used for RT response assessment. Additionally, issues and limits of current works, as well as challenges and potential future research directions, will also be discussed.

Cone-beam CT delta-radiomics to predict genitourinary toxicities and international prostate symptom of prostate cancer patients: a pilot study.

For prostate cancer (PCa) patients treated with definitive radiotherapy (RT), acute and late RT-related genitourinary (GU) toxicities adversely impact disease-specific quality of life. Early warning of potential RT toxicities can prompt interventions that may prevent or mitigate future adverse events. During intensity modulated RT (IMRT) of PCa, daily cone-beam computed tomography (CBCT) images are used to improve treatment accuracy through image guidance. This work investigated the performance of CBCT-based delta-radiomic features (DRF) models to predict acute and sub-acute International Prostate Symptom Scores (IPSS) and Common Terminology Criteria for Adverse Events (CTCAE) version 5 GU toxicity grades for 50 PCa patients treated with definitive RT. Delta-radiomics models were built using logistic regression, random forest for feature selection, and a 1000 iteration bootstrapping leave one analysis for cross validation. To our knowledge, no prior studies of PCa have used DRF models based on daily CBCT images. AUC of 0.83 for IPSS and greater than 0.7 for CTCAE grades were achieved as early as week 1 of treatment. DRF extracted from CBCT images showed promise for the development of models predictive of RT outcomes. Future studies will include using artificial intelligence and machine learning to expand CBCT sample sizes available for radiomics analysis.

Knowledge-Based Planning for Robustly Optimized Intensity-Modulated Proton Therapy of Head and Neck Cancer Patients.

PURPOSE: To assess the performance of a proton-specific knowledge-based planning (KBP) model in the creation of robustly optimized intensity-modulated proton therapy (IMPT) plans for treatment of advanced head and neck (HN) cancer patients. METHODS: Seventy-three patients diagnosed with advanced HN cancer previously treated with volumetric modulated arc therapy (VMAT) were selected and replanned with robustly optimized IMPT. A proton-specific KBP model, RapidPlanPT (RPP), was generated using 53 patients (20 unilateral cases and 33 bilateral cases). The remaining 20 patients (10 unilateral and 10 bilateral cases) were used for model validation. The model was validated by comparing the target coverage and organ at risk (OAR) sparing in the RPP-generated IMPT plans with those in the expert plans. To account for the robustness of the plan, all uncertainty scenarios were included in the analysis. RESULTS: All the RPP plans generated were clinically acceptable. For unilateral cases, RPP plans had higher CTV_primary V100 (1.59% ± 1.24%) but higher homogeneity index (HI) (0.7 ± 0.73) than had the expert plans. In addition, the RPP plans had better ipsilateral cochlea Dmean (-5.76 ± 6.11 Gy), with marginal to no significant difference between RPP plans and expert plans for all other OAR dosimetric indices. For the bilateral cases, the V100 for all clinical target volumes (CTVs) was higher for the RPP plans than for the expert plans, especially the CTV_primary V100 (5.08% ± 3.02%), with no significant difference in the HI. With respect to OAR sparing, RPP plans had a lower spinal cord Dmax (-5.74 ± 5.72 Gy), lower cochlea Dmean (left, -6.05 ± 4.33 Gy; right, -4.84 ± 4.66 Gy), lower left and right parotid V20Gy (left, -6.45% ± 5.32%; right, -6.92% ± 3.45%), and a lower integral dose (-0.19 ± 0.19 Gy). However, RPP plans increased the Dmax in the body outside of CTV (body-CTV) (1.2 ± 1.43 Gy), indicating a slightly higher hotspot produced by the RPP plans. CONCLUSION: IMPT plans generated by a broad-scope RPP model have a quality that is, at minimum, comparable with, and at times superior to, that of the expert plans. The RPP plans demonstrated a greater robustness for CTV coverage and better sparing for several OARs.

Online Magnetic Resonance-Guided Radiotherapy (oMRgRT) for Gynecological Cancers.

Radiation therapy (RT) is increasingly being used in gynecological cancer management. RT delivered with curative or palliative intent can be administered alone or combined with chemotherapy or surgery. Advanced treatment planning and delivery techniques such as intensity-modulated radiation therapy, including volumetric modulated arc therapy, and image-guided adaptive brachytherapy allow for highly conformal radiation dose delivery leading to improved tumor control rates and less treatment toxicity. Quality on-board imaging that provides accurate visualization of target and surrounding organs at risk is a critical feature of these advanced techniques. As soft tissue contrast resolution is superior with magnetic resonance imaging (MRI) compared to other imaging modalities, MRI has been used increasingly to delineate tumor from adjacent soft tissues and organs at risk from initial diagnosis to tumor response evaluation. Gynecological cancers often have poor contrast resolution compared to the surrounding tissues on computed tomography scan, and consequently the benefit of MRI is high. One example is in management of locally advanced cervix cancer where adaptive MRI guidance has been broadly implemented for adaptive brachytherapy. The role of MRI for external beam RT is also steadily increasing. MRI information is being used for treatment planning, predicting, and monitoring position shifts and accounting for tissue deformation and target regression during treatment. The recent clinical introduction of online MRI-guided radiation therapy (oMRgRT) could be the next step in high-precision RT. This technology provides a tool to take full advantage of MRI not only at the time of initial treatment planning but as well as for daily position verification and online plan adaptation. Cervical, endometrial, vaginal, and oligometastatic ovarian cancers are being treated on MRI linear accelerator systems throughout the world. This review summarizes the current state, early experience, ongoing trials, and future directions of oMRgRT in the management of gynecological cancers.