Detection of Interfractional Morphological Changes in Proton Therapy: A Simulation and In Vivo Study With the INSIDE In-Beam PET

In particle therapy, the uncertainty of the delivered particle range during the patient irradiation limits the optimization of the treatment planning. Therefore, an in vivo treatment verification device is required, not only to improve the plan robustness, but also to detect significant interfractional morphological changes during the treatment itself. In this article, an effective and robust analysis to detect regions with a significant range discrepancy is proposed. This study relies on an in vivo treatment verification by means of in-beam Positron Emission Tomography (PET) and was carried out with the INSIDE system installed at the National Center of Oncological Hadrontherapy (CNAO) in Pavia, which is under clinical testing since July 2019. Patients affected by head-and-neck tumors treated with protons have been considered. First, in order to tune the analysis parameters, a Monte Carlo (MC) simulation was carried out to reproduce a patient who required a replanning because of significant morphological changes found during the treatment. Then, the developed approach was validated on the experimental measurements of three patients recruited for the INSIDE clinical trial (ClinicalTrials.gov ID: NCT03662373), showing the capability to estimate the treatment compliance with the prescription both when no morphological changes occurred and when a morphological change did occur, thus proving to be a promising tool for clinicians to detect variations in the patients treatments.

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In Vivo Treatment Verification *

Proton Therapy Physics ◽

10.1201/b22053-22 ◽

2018 ◽

pp. 643-677

Author(s):

Katia Parodi

Keyword(s):

Treatment Verification ◽

In Vivo Treatment

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Validation and noninvasive kinetic modeling of [11C]UCB-J PET imaging in mice

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x19864081 ◽

2019 ◽

Vol 40 (6) ◽

pp. 1351-1362 ◽

Cited By ~ 5

Author(s):

Daniele Bertoglio ◽

Jeroen Verhaeghe ◽

Alan Miranda ◽

Istvan Kertesz ◽

Klaudia Cybulska ◽

...

Keyword(s):

Pet Imaging ◽

Neurodegenerative Disorder ◽

Input Function ◽

Dependent Manner ◽

In Vivo Metabolism ◽

Promising Tool ◽

Positron Emission ◽

Synaptic Pathology

Synaptic pathology is associated with several brain disorders, thus positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) using the radioligand [11C]UCB-J may provide a tool to measure synaptic alterations. Given the pivotal role of mouse models in understanding neuropsychiatric and neurodegenerative disorders, this study aims to validate and characterize [11C]UCB-J in mice. We performed a blocking study to verify the specificity of the radiotracer to SV2A, examined kinetic models using an image-derived input function (IDIF) for quantification of the radiotracer, and investigated the in vivo metabolism. Regional TACs during baseline showed rapid uptake of [11C]UCB-J into the brain. Pretreatment with levetiracetam confirmed target engagement in a dose-dependent manner. VT (IDIF) values estimated with one- and two-tissue compartmental models (1TCM and 2TCM) were highly comparable (r=0.999, p < 0.0001), with 1TCM performing better than 2TCM for K1 (IDIF). A scan duration of 60 min was sufficient for reliable VT (IDIF) and K1 (IDIF) estimations. In vivo metabolism of [11C]UCB-J was relatively rapid, with a parent fraction of 22.5 ± 4.2% at 15 min p.i. In conclusion, our findings show that [11C]UCB-J selectively binds to SV2A with optimal kinetics in the mouse representing a promising tool to noninvasively quantify synaptic density in comparative or therapeutic studies in neuropsychiatric and neurodegenerative disorder models.

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A method for in vivo treatment verification of IMRT and VMAT based on electronic portal imaging device

Radiation Oncology ◽

10.1186/s13014-021-01953-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Jun Zhang ◽

Xiuqing Li ◽

Miaomiao Lu ◽

Qilin Zhang ◽

Xile Zhang ◽

...

Keyword(s):

Quality Assurance ◽

Radiation Therapy ◽

Measurement Data ◽

Patient Specific ◽

Imaging Device ◽

Portal Imaging ◽

Treatment Verification ◽

Electronic Portal Imaging ◽

In Vivo Treatment

Abstract Background Intensity-modulated radiation therapy (IMRT) and volume-modulated arc therapy (VMAT) are rather complex treatment techniques and require patient-specific quality assurance procedures. Electronic portal imaging devices (EPID) are increasingly used in the verification of radiation therapy (RT). This work aims to develop a novel model to predict the EPID transmission image (TI) with fluence maps from the RT plan. The predicted TI is compared with the measured TI for in vivo treatment verification. Methods The fluence map was extracted from the RT plan and corrections of penumbra, response, global field output, attenuation, and scatter were applied before the TI was calculated. The parameters used in the model were calculated separately for central axis and off-axis points using a series of EPID measurement data. Our model was evaluated using a CIRS thorax phantom and 20 clinical plans (10 IMRT and 10 VMAT) optimized for head and neck, breast, and rectum treatments. Results Comparisons of the predicted and measured images were carried out using a global gamma analysis of 3%/2 mm (10% threshold) to validate the accuracy of the model. The gamma pass rates for IMRT and VMAT were greater than 97.2% and 94.5% at 3%/2 mm, respectively. Conclusion We have developed an accurate and straightforward EPID-based quality assurance model that can potentially be used for in vivo treatment verification of the IMRT and VMAT delivery.

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FLARIM v2.0, an improved method to quantify transcript-ribosome interactions in vivo in the adult Drosophila brain

10.1101/2021.08.13.456301 ◽

2021 ◽

Author(s):

Petra Richer ◽

Sean D Speese ◽

Mary A Logan

Keyword(s):

Immune Response ◽

Morphological Changes ◽

Immune Gene ◽

Promising Tool ◽

Matrix Metalloproteinase 1 ◽

New Variant ◽

Wide Range ◽

Drosophila Brain

Neural injury triggers striking immune reactions from glial cells, including significant transcriptional and morphological changes, but it is unclear how these events are coordinated to mount an effective immune response. Here, we present a new variant of the Fluorescence assay to detect ribosome interactions with mRNA (FLARIM), which we term FLARIM v2.0, to visualize single immune gene transcripts and association with ribosomes in glia responding to neurodegeneration. Specifically, using an in vivo axotomy assay in Drosophila, we show that matrix metalloproteinase-1 (Mmp-1) mRNAs and associated ribosomes are detected in distal processes of reactive glia where they are actively engulfing degenerating axonal material, suggesting that local translation is an important component of the glial immune response to axotomy. This work also validates our enhanced FLARIM assay as a promising tool to investigate mechanisms of mRNA transport and translation in a wide range of in vitro and in vivo paradigms.

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