Patient-specific microdosimetry: a proof of concept
Bibliographic record
Abstract
Abstract 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 including <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mi>f</mml:mi> <mml:mrow> <mml:mo stretchy="false">(</mml:mo> <mml:mi>y</mml:mi> <mml:mo stretchy="false">)</mml:mo> </mml:mrow> </mml:math> and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mi mathvariant="normal">d</mml:mi> <mml:mrow> <mml:mo stretchy="false">(</mml:mo> <mml:mi>y</mml:mi> <mml:mo stretchy="false">)</mml:mo> </mml:mrow> </mml:math> were determined for <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mmultiscripts> <mml:mi mathvariant="normal">C</mml:mi> <mml:none/> <mml:none/> <mml:mprescripts/> <mml:none/> <mml:mrow> <mml:mn>60</mml:mn> </mml:mrow> </mml:mmultiscripts> <mml:mi mathvariant="normal">o</mml:mi> <mml:mo>,</mml:mo> <mml:mspace width=".25em"/> <mml:mmultiscripts> <mml:mi mathvariant="normal">I</mml:mi> <mml:none/> <mml:none/> <mml:mprescripts/> <mml:none/> <mml:mrow> <mml:mn>192</mml:mn> </mml:mrow> </mml:mmultiscripts> <mml:mi mathvariant="normal">r</mml:mi> <mml:mo>,</mml:mo> <mml:mspace width=".25em"/> <mml:mmultiscripts> <mml:mi mathvariant="normal">Y</mml:mi> <mml:none/> <mml:none/> <mml:mprescripts/> <mml:none/> <mml:mrow> <mml:mn>169</mml:mn> </mml:mrow> </mml:mmultiscripts> <mml:mi mathvariant="normal">b</mml:mi> </mml:math> and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mmultiscripts> <mml:mi mathvariant="normal">I</mml:mi> <mml:none/> <mml:none/> <mml:mprescripts/> <mml:none/> <mml:mrow> <mml:mn>125</mml:mn> </mml:mrow> </mml:mmultiscripts> </mml:math> in 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 model <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mrow> <mml:mover accent="true"> <mml:mi>y</mml:mi> <mml:mo>¯</mml:mo> </mml:mover> </mml:mrow> <mml:mrow> <mml:mi mathvariant="normal">f</mml:mi> </mml:mrow> </mml:msub> </mml:math> or <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mrow> <mml:mover accent="true"> <mml:mi>y</mml:mi> <mml:mo>¯</mml:mo> </mml:mover> </mml:mrow> <mml:mrow> <mml:mi mathvariant="normal">d</mml:mi> </mml:mrow> </mml:msub> <mml:mspace width=".25em"/> </mml:math> for the lower energy sources investigated, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mmultiscripts> <mml:mi mathvariant="normal">Y</mml:mi> <mml:none/> <mml:none/> <mml:mprescripts/> <mml:none/> <mml:mrow> <mml:mn>169</mml:mn> </mml:mrow> </mml:mmultiscripts> <mml:mi mathvariant="normal">b</mml:mi> </mml:math> and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mmultiscripts> <mml:mi mathvariant="normal">I</mml:mi> <mml:none/> <mml:none/> <mml:mprescripts/> <mml:none/> <mml:mrow> <mml:mn>125</mml:mn> </mml:mrow> </mml:mmultiscripts> <mml:mo>.</mml:mo> </mml:math> The higher energy sources investigated, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mmultiscripts> <mml:mi mathvariant="normal">C</mml:mi> <mml:none/> <mml:none/> <mml:mprescripts/> <mml:none/> <mml:mrow> <mml:mn>60</mml:mn> </mml:mrow> </mml:mmultiscripts> <mml:mi mathvariant="normal">o</mml:mi> </mml:math> and
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".