Patient-specific microdosimetry: a proof of concept.

Microscopic energy deposition distributions from ionizing radiation vary depending on biological target size and are used to predict the biological effects of an irradiation. Ionizing radiation is thought to kill cells or inhibit the cell cycle mainly by damaging DNA in the cell nucleus. The size of cells and nuclei depends on tissue type, cell cycle, and malignancy, all of which vary between patients. The aim of this study was to develop methods to perform patient-specific microdosimetry, that being, determining microdosimetric quantities in volumes that correspond to the sizes of cells and nuclei observed in a patient's tissue. A histopathological sample extracted from a stage I lung adenocarcinoma patient was analyzed. A pouring simulation was used to generate a three-dimensional tissue model from cell and nucleus size information determined from the histopathological sample. Microdosimetric distributions includingf(y)andd(y)were determined forC60o,I192r,Y169bandI125in a patient-specific model containing a distribution of cell and nucleus sizes. Fixed radius models and a summation method were compared to the full patient-specific model to evaluate their suitability for fast determination of patient-specific microdosimetric parameters. In the summation method,f(y)from many fixed radii models are summed. Fixed radius models do not provide a close approximation of the full patient-specific modely¯fory¯dfor the lower energy sources investigated,Y169bandI125.The higher energy sources investigated,C60oandI192rare less sensitive to target size variation thanY169bandI125.The summation method yields the most accurate approximation of the full modeld(y)for all radioisotopes investigated. The use of a summation method allows for the computation of patient-specific microdosimetric distributions with the computing power of a personal computer. With appropriate biological inputs the microdosimetric distributions computed using these methods can yield a patient-specific relative biological effectiveness as part of a multiscale treatment planning approach.

Development of patient-specific 3D models from histopathological samples for applications in radiation therapy.

The biological effects of ionizing radiation depend on the tissue, tumor type, radiation quality, and patient-specific factors. Inter-patient variation in cell/nucleus size may influence patient-specific dose response. However, this variability in dose response is not well investigated due to lack of available cell/nucleus size data. The aim of this study was to develop methods to derive cell/nucleus size distributions from digital images of 2D histopathological samples and use them to build digital 3D models for use in cellular dosimetry. Nineteen of sixty hematoxylin and eosin stained lung adenocarcinoma samples investigated passed exclusion criterion to be analyzed in the study. A difference of gaussians blob detection algorithm was used to identify nucleus centers and quantify cell spacing. Hematoxylin content was measured to determine nucleus radius. Pouring simulations were conducted to generate one-hundred 3D models containing volumes of equivalent cell spacing and nuclei radius to those in histopathological samples. The nuclei radius distributions of non-tumoral and cancerous regions appearing in the same slide were significantly different (p < 0.01) in all samples analyzed. The median nuclear-cytoplasmic ratio was 0.36 for non-tumoral cells and 0.50 for cancerous cells. The average cellular and nucleus packing densities in the 3D models generated were 65.9% (SD: 1.5%) and 13.3% (SD: 0.3%) respectively. Software to determine cell spacing and nuclei radius from histopathological samples was developed. 3D digital tissue models containing volumes with equivalent cell spacing, nucleus radius, and packing density to cancerous tissues were generated.

A new delivery system to resolve dosimetric issues in intravascular brachytherapy.

PURPOSE: Renewed interest is being expressed in intravascular brachytherapy (IVBT). A number of unresolved issues exist in the discipline. Providing a homogeneous and adequate dose to the target remains difficult in IVBT. The guidewire that delivers the device to the target, arterial plaques, and stent struts are all known to reduce the dose delivered to target. The viability and efficacy of a proposed IVBT delivery system designed to resolve the issue of guidewire attenuation is evaluated and compared to that of a popular and commercially available IVBT device. METHODS AND MATERIALS: Monte Carlo simulations are conducted to determine distributions of absorbed dose around an existing and proposed IVBT delivery system. RESULTS: For the Novoste Beta-Cath 3.5F (TeamBest®), dose in water varies by 10% as a function of angle in the plane perpendicular to the delivery catheter due to off-centering of seeds in the catheter. Dose is reduced by 52% behind a stainless steel guidewire and 64% behind a guidewire, arterial plaque, and stent strut for the Novoste Beta-Cath 3.5F. Dose is not perturbed by the presence of a guidewire for the proposed device and is reduced by 46% by an arterial plaque and stent strut. CONCLUSIONS: Dose attenuation by guidewire is likely the single greatest source of dose attenuation in IVBT in terms of absolute dose reduction and is greater than previously reported for the Novoste Beta-Cath 3.5F. The Novoste Beta-Cath 3.5F delivers an inhomogeneous dose to target. A delivery system is proposed, which resolves the issue of guidewire attenuation in IVBT and should reduce treatment times.