Precision Radiotherapy for Small Animal Research

Matinfar, Mohammad; Iordachita, Iulian; Ford, Eric; Wong, John W.; Kazanzides, Peter

doi:10.1007/978-3-540-85990-1_74

Cited by 15 publications

(11 citation statements)

References 6 publications

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“…Several alternatives are commercially available that allow one to perform image-guided small animal irradiation. Furthermore, CT-guided focal irradiation systems can also be built in house, as was the case with the system used for these studies at Johns Hopkins [29][30][31][32][33]35 .…”

Section: Discussionmentioning

confidence: 99%

“…However, previous radiological approaches have generally targeted large areas, or often unintentionally also targeted multiple brain areas where neurogenesis has been reported, making it difficult to unambiguously associate any behavioral defects observed with defects in specific neural progenitor populations. The capability for more targeted irradiation is provided by radiological platforms that combine computer tomography-guided imaging with focal beam irradiation (CFIR) delivery to enable precise anatomical targeting [29][30][31][32][33][34][35][36] . Radiation beams as small as 0.5 mm in diameter are available to target specific neural progenitor populations 35 .…”

Section: Introductionmentioning

confidence: 99%

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Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition

Lee

Salvatierra

Velarde

et al. 2013

JoVE

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The functional characterization of adult-born neurons remains a significant challenge. Approaches to inhibit adult neurogenesis via invasive viral delivery or transgenic animals have potential confounds that make interpretation of results from these studies difficult. New radiological tools are emerging, however, that allow one to noninvasively investigate the function of select groups of adult-born neurons through accurate and precise anatomical targeting in small animals. Focal ionizing radiation inhibits the birth and differentiation of new neurons, and allows targeting of specific neural progenitor regions. In order to illuminate the potential functional role that adult hypothalamic neurogenesis plays in the regulation of physiological processes, we developed a noninvasive focal irradiation technique to selectively inhibit the birth of adult-born neurons in the hypothalamic median eminence. We describe a method for Computer tomography-guided focal irradiation (CFIR) delivery to enable precise and accurate anatomical targeting in small animals. CFIR uses three-dimensional volumetric image guidance for localization and targeting of the radiation dose, minimizes radiation exposure to nontargeted brain regions, and allows for conformal dose distribution with sharp beam boundaries. This protocol allows one to ask questions regarding the function of adult-born neurons, but also opens areas to questions in areas of radiobiology, tumor biology, and immunology. These radiological tools will facilitate the translation of discoveries at the bench to the bedside.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition

Lee

Salvatierra

Velarde

et al. 2013

JoVE

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“…1 Microirradiators enable exploration of the efficacy of novel radiation treatment approaches by providing the capability to reproduce realistic treatment delivery in small animal models. [2][3][4][5][6][7] Investigation of the efficacy and biological radio-response from new radiation treatments rely on the use of these small animal models before reaching the clinic. Preclinical studies aim to highlight the biological mechanisms governing radiotherapy response in many radiation applications.…”

Section: Introductionmentioning

confidence: 99%

Investigating the accuracy of microstereotactic‐body‐radiotherapy utilizing anatomically accurate 3D printed rodent‐morphic dosimeters

et al. 2015

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Purpose: Sophisticated small animal irradiators, incorporating cone-beam-CT image-guidance, have recently been developed which enable exploration of the efficacy of advanced radiation treatments in the preclinical setting. Microstereotactic-body-radiation-therapy (microSBRT) is one technique of interest, utilizing field sizes in the range of 1-15 mm. Verification of the accuracy of microSBRT treatment delivery is challenging due to the lack of available methods to comprehensively measure dose distributions in representative phantoms with sufficiently high spatial resolution and in 3 dimensions (3D). This work introduces a potential solution in the form of anatomically accurate rodent-morphic 3D dosimeters compatible with ultrahigh resolution (0.3 mm 3 ) optical computed tomography (optical-CT) dose read-out. Methods: Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from contours defined on x-ray CT data sets of rats and mice, and using these molds to create tissue-equivalent radiochromic 3D dosimeters from Presage. Anatomically accurate spines were incorporated into some dosimeters, by first 3D printing the spine mold, then forming a high-Z bone equivalent spine insert. This spine insert was then set inside the tissue equivalent body mold. The high-Z spinal insert enabled representative cone-beam CT IGRT targeting. On irradiation, a linear radiochromic change in optical-density occurs in the dosimeter, which is proportional to absorbed dose, and was read out using optical-CT in high-resolution (0.5 mm isotropic voxels). Optical-CT data were converted to absolute dose in two ways: (i) using a calibration curve derived from other Presage dosimeters from the same batch, and (ii) by independent measurement of calibrated dose at a point using a novel detector comprised of a yttrium oxide based nanocrystalline scintillator, with a submillimeter active length. A microSBRT spinal treatment was delivered consisting of a 180• continuous arc at 225 kVp with a 20 × 10 mm field size. Dose response was evaluated using both the Presage/optical-CT 3D dosimetry system described above, and independent verification in select planes using EBT2 radiochromic film placed inside rodent-morphic dosimeters that had been sectioned in half. Results: Rodent-morphic 3D dosimeters were successfully produced from Presage radiochromic material by utilizing 3D printed molds of rat CT contours. The dosimeters were found to be compatible with optical-CT dose readout in high-resolution 3D (0.5 mm isotropic voxels) with minimal artifacts or noise. Cone-beam CT image guidance was possible with these dosimeters due to sufficient contrast between high-Z spinal inserts and tissue equivalent Presage material (CNR ∼10 on CBCT images). Dose at isocenter measured with optical-CT was found to agree with nanoscintillator measurement to within 2.8%. Maximum dose in line profiles taken through Presage and film dose slices agreed within 3%, with FWHM measurements through each profile found to agree within 2%. Conclusions: T...

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“…We also investigated FDG-PET’s ability, using several analytical approaches, to demonstrate a tumor’s internal heterogeneous distribution of viable tumor tissues in addition to delineation of the total tumor volume. We would like to quantify the viable and necrotic regions within a tumor to facilitate animal radiotherapy planning studies seeking dose efficiency and reduction or tumor necrosis targeted radiotherapy [10, 11]. …”

Section: Introductionmentioning

confidence: 99%

Optimal definition of biological tumor volume using positron emission tomography in an animal model

Wang

Huso

et al. 2015

EJNMMI Res

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BackgroundThe goal of the study is to investigate 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)’s ability to delineate the viable portion of a tumor in an animal model using cross-sectional histology as the validation standard.MethodsSyngeneic mammary tumors were grown in female Lewis rats. Macroscopic histological images of the transverse tumor sections were paired with their corresponding FDG micro-PET slices of the same cranial-caudal location to form 51 pairs of co-registered images. A binary classification system based on four FDG-PET tumor contouring methods was applied to each pair of images: threshold based on (1) percentage of maximum tumor voxel counts (Cmax), (2) percentage of tumor peak voxel counts (Cpeak), (3) multiples of liver mean voxel counts (Cliver) derived from PERCIST, and (4) an edge-detection-based automated contouring system. The sensitivity, which represented the percentage of viable tumor areas correctly delineated by the gross tumor area (GTA) generated from a particular tumor contouring method, and the ratio (expressed in percentage) of the overestimated areas of a gross tumor area (GTAOE)/whole tumor areas on the macroscopic histology (WTAH), which represented how much a particular GTA extended into the normal structures surrounding the primary tumor target, were calculated.ResultsThe receiver operating characteristic curves of all pairs of FDG-PET images have a mean area under the curve value of 0.934 (CI of 0.911–0.954), for representing how well each contouring method accurately delineated the viable tumor area. FDG-PET single value threshold tumor contouring based on 30 and 35 % of tumor Cmax or Cpeak and 6 × Cliver + 2 × SD achieved a sensitivity greater than 90 % with a GTAOE/WTAH ratio less than 10 %. Contouring based on 50 % of Cmax or Cpeak had a much lower sensitivity of 67.2–75.6 % with a GTAOE/WTAH ratio of 1.1–1.7 %. Automated edge detection was not reliable in this system.ConclusionsSingle-value-threshold tumor contouring using 18F-FDG-PET is able to accurately delineate the viable portion of a tumor. 30 and 35 % of Cmax, 30 and 35 % of Cpeak, and 6 × Cliver + 2 × SD are three appropriate threshold values to delineate viable tumor volume in our animal model. The commonly used threshold value of 50 % of Cmax or Cpeak failed to detect one third of the viable tumor volume in our model.

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Precision Radiotherapy for Small Animal Research

Cited by 15 publications

References 6 publications

Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition

Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition

Investigating the accuracy of microstereotactic‐body‐radiotherapy utilizing anatomically accurate 3D printed rodent‐morphic dosimeters

Optimal definition of biological tumor volume using positron emission tomography in an animal model

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