Feasibility of a Novel Sparse Orthogonal Collimator–Based Preclinical Total Marrow Irradiation for Enhanced Dosimetric Conformality

Abdelhamid, Amr M H; Jiang, Lu; Zuro, Darren; Liu, An; Madabushi, Srideshikan Sargur; Ghimire, Hemendra; Wong, Jeffrey Y.C.; Saldi, Simonetta; Fulcheri, C.; Zucchetti, C.; Pierini, Antonio; Sheng, Ke; Aristei, Cynthia; Song, Hui

doi:10.3389/fonc.2022.941814

Cited by 4 publications

(3 citation statements)

References 35 publications

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“…The run time of sIMRT plans for the TMI case is relatively long at 20 min, mainly due to the PTV size and shape complexity. However, the delivery time is still shorter than the reported 3D-TMI preclinical method taking 25 min (Abdelhamid et al 2022) to deliver. The treatment planning time for sIMRT is approximately 25 min, which compares favorably with the 3D-TMI method taking∼1 h. The longer planning time is still favorable (delivering desired dose to specific organs) compared to the tedious manual lead or copper compensator based setup (Hui et al 2017).…”

Section: Discussionmentioning

confidence: 89%

An efficient rectangular optimization method for sparse orthogonal collimator based small animal irradiation

Jiang¹,

Lyu²,

Abdelhamid³

et al. 2022

Phys. Med. Biol.

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Objective: Intensity-modulated radiotherapy (IMRT) is widely used in clinical radiotherapy, treating varying malignancies with conformal doses. As the test field for clinical translation, preclinical small animal experiments need to mimic the human radiotherapy condition, including IMRT. However, small animal IMRT is a systematic challenge due to the lack of corresponding hardware and software for miniaturized targets. Approach: The sparse orthogonal collimators (SOC) based on the direct rectangular aperture optimization (RAO) substantially simplified the hardware for miniaturization. This study investigates and evaluates a significantly improved RAO algorithm for complex mouse irradiation using SOC. Because the Kronecker product representation of the rectangular aperture is the main limitation of the computational performance, we reformulated matrix multiplication in the data fidelity term using multiplication with small matrices instead of the Kronecker product of the dose loading matrices. Solving the optimization problem was further accelerated using the Fast Iterative Shrinkage-Thresholding Algorithm (FISTA). Main results: Four mouse cases, including a liver, a brain tumor, a concave U-target, and a complex total marrow irradiation (TMI) case, were included in this study with manually delineated targets and OARs. Seven coplanar-field SOC IMRT plans were compared with IMRT plans using an idealistic multi-leaf collimator (MLC). For the first three cases with simpler and smaller targets, the differences between SOC plans and MLC plans in the planning target volumes (PTV) statistics are within 1%. For the TMI case, the SOC plans are superior in reducing hot spots (also termed Dmax) of PTV, kidneys, lungs, heart, and bowel by 20.5%, 31.5%, 24.67%, 20.13%, and 17.78%, respectively. On average, in four cases in this study, the SOC plan conformity is comparable to that of the MLC’s with lightly increased R50 and Integral Dose by 2.23% and 2.78%. Significance: The significantly improved SOC optimization method allows fast plan creation in under 1 minute for smaller targets and makes complex TMI planning feasible while achieving comparable dosimetry to hypothetical IMRT with a theoretical MLC.

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Section: Discussionmentioning

confidence: 89%

An efficient rectangular optimization method for sparse orthogonal collimator based small animal irradiation

Jiang¹,

Lyu²,

Abdelhamid³

et al. 2022

Phys. Med. Biol.

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“…In the future, we will develop 3D sections of an entire lung to identify high dose and low dose region. Also, we recently simulated a novel sparse orthogonal collimator–based intensity modulated preclinical TMI, which will significantly reduce radiation dose to lungs and kidney and enhance dosimetric conformality to the skeletal system ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

Total marrow irradiation reduces organ damage and enhances tissue repair with the potential to increase the targeted dose of bone marrow in both young and old mice

Lim

Madabushi²,

Vishwasrao³

et al. 2022

Front. Oncol.

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Total body irradiation (TBI) is a commonly used conditioning regimen for hematopoietic stem cell transplant (HCT), but dose heterogeneity and long-term organ toxicity pose significant challenges. Total marrow irradiation (TMI), an evolving radiation conditioning regimen for HCT can overcome the limitations of TBI by delivering the prescribed dose targeted to the bone marrow (BM) while sparing organs at risk. Recently, our group demonstrated that TMI up to 20 Gy in relapsed/refractory AML patients was feasible and efficacious, significantly improving 2-year overall survival compared to the standard treatment. Whether such dose escalation is feasible in elderly patients, and how the organ toxicity profile changes when switching to TMI in patients of all ages are critical questions that need to be addressed. We used our recently developed 3D image-guided preclinical TMI model and evaluated the radiation damage and its repair in key dose-limiting organs in young (~8 weeks) and old (~90 weeks) mice undergoing congenic bone marrow transplant (BMT). Engraftment was similar in both TMI and TBI-treated young and old mice. Dose escalation using TMI (12 to 16 Gy in two fractions) was well tolerated in mice of both age groups (90% survival ~12 Weeks post-BMT). In contrast, TBI at the higher dose of 16 Gy was particularly lethal in younger mice (0% survival ~2 weeks post-BMT) while old mice showed much more tolerance (75% survival ~13 weeks post-BMT) suggesting higher radio-resistance in aged organs. Histopathology confirmed worse acute and chronic organ damage in mice treated with TBI than TMI. As the damage was alleviated, the repair processes were augmented in the TMI-treated mice over TBI as measured by average villus height and a reduced ratio of relative mRNA levels of amphiregulin/epidermal growth factor (areg/egf). These findings suggest that organ sparing using TMI does not limit donor engraftment but significantly reduces normal tissue damage and preserves repair capacity with the potential for dose escalation in elderly patients.

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“…Nevertheless, the current workflow for image-guided small animal irradiator treatment planning requires manual delineation of organs and tumors, which is often impractical given the constraints in time, resources, and expertise within the pre-clinical domain [23,24]. Another challenge is the low contrast of small animal imaging systems, which is particularly problematic when delineating morphologically complex and low-native-contrast abdominal organs, such as the spleen.…”

Section: Introductionmentioning

confidence: 99%

Anatomy-constrained synthesis for spleen segmentation improvement in unpaired mouse micro-CT scans with 3D CycleGAN

Jiang,

Xu,

Sheng

2024

Biomed. Phys. Eng. Express

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Objective: Auto-segmentation in mouse micro-CT enhances the efficiency and consistency of preclinical experiments but often struggles with low-native-contrast and morphologically complex organs, such as the spleen, resulting in poor segmentation performance. While CT contrast agents can improve organ conspicuity, their use complicates experimental protocols and reduces feasibility. We developed a 3D Cycle Generative Adversarial Network (CycleGAN) incorporating anatomy-constrained U-Net models to leverage contrast-enhanced CT (CECT) insights to improve unenhanced native CT (NACT) segmentation. Approach: We employed a standard CycleGAN with an anatomical loss function to synthesize virtual CECT images from unpaired NACT scans at two different resolutions. Prior to training, two U-Nets were trained to automatically segment six major organs in NACT and CECT datasets, respectively. These pretrained 3D U-Nets were integrated during the CycleGAN training, segmenting synthetic images, and comparing them against ground truth annotations. The compound loss within the CycleGAN maintained anatomical fidelity. Full image processing was achieved for low-resolution datasets, while high-resolution datasets employed a patch-based method due to GPU memory constraints. Automated segmentation was applied to original NACT and synthetic CECT scans to evaluate CycleGAN performance using the Dice Similarity Coefficient (DSC) and the 95th percentile Hausdorff Distance (HD95p).Main Results:High-resolution scans showed improved auto-segmentation, with an average DSC increase from 0.728 to 0.773 and a reduced HD95p from 1.19 mm to 0.94 mm. Low-resolution scans benefited more from synthetic contrast, showing a DSC increase from 0.586 to 0.682 and an HD95p reduction from 3.46 mm to 1.24 mm. Significance:Implementing CycleGAN to synthesize CECT scans substantially improved the visibility of the mouse spleen, leading to more precise auto-segmentation. This approach shows the potential in preclinical imaging studies where contrast agent use is impractical.

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Feasibility of a Novel Sparse Orthogonal Collimator–Based Preclinical Total Marrow Irradiation for Enhanced Dosimetric Conformality

Cited by 4 publications

References 35 publications

An efficient rectangular optimization method for sparse orthogonal collimator based small animal irradiation

An efficient rectangular optimization method for sparse orthogonal collimator based small animal irradiation

Total marrow irradiation reduces organ damage and enhances tissue repair with the potential to increase the targeted dose of bone marrow in both young and old mice

Anatomy-constrained synthesis for spleen segmentation improvement in unpaired mouse micro-CT scans with 3D CycleGAN

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