Validation of Automatic Target Volume Definition as Demonstrated for11 C-Choline PET/CT of Human Prostate Cancer Using Multi-modality Fusion Techniques

Rationale and Objectives

Positron emission tomography (PET) is actively investigated to aid in target volume definition for radiation therapy. The objectives of this study were to apply an automatic computer algorithm to compute target volumes and to validate the algorithm using histologic data from real human prostate cancer.

Materials and Methods

Various modalities for prostate imaging were performed. In vivo imaging included T2 3-T magnetic resonance imaging and 11 C-choline PET. Ex vivo imaging included 3-T magnetic resonance imaging, histology, and block face photos of the prostate specimen. A novel registration method based on mutual information and thin-plate splines was applied to all modalities. Once PET is registered with histology, a voxel-by-voxel comparison between PET and histology is possible. A thresholding technique based on various fractions of the maximum standardized uptake value in the tumor was applied, and the respective computed threshold volume on PET was compared with histologic truth.

Results

Sixteen patients whose primary tumor volumes ranged from 1.2 to 12.6 cm 3 were tested. PET has low spatial resolution, so only tumors > 4 cm 3 were considered. Four cases met this criterion. A threshold value of 60% of the 11 C-choline maximum standardized uptake value resulted in the highest volume overlap between threshold volume on PET and histology. Medial axis distances between threshold volume on PET and histology showed a mean error of 7.7 ± 5.2 mm.

Conclusions

This is a proof-of-concept study demonstrating for the first time that histology-guided thresholding on PET can delineate tumor volumes in real human prostate cancer.

Substantial technological progress involving intensity-modulated radiotherapy and three-dimensional planning of brachytherapy for prostate cancer has enabled the delivery of radiation treatment with high geometric precision . Radiation oncology refers to the volume, including the entire tumor and its microscopic extensions, as the clinical target volume. The general goal of radiation therapy is to maximize the dose to the target volume while minimizing damage to surrounding normal tissues. With advances in image guidance, accurate target volume definition is becoming even more important, because highly differential radiation doses can only be justified when the planning target volume is precisely matched with the “true” tumor volume.

Currently, target volume definition is based on anatomic imaging with magnetic resonance imaging (MRI) or computed tomography (CT). Although anatomic imaging can convey structural information with high resolution, it suffers from a serious limitation. Anatomic imaging portrays the tumor volume using variation of tissue density (for CT) or relaxation properties (for MRI) using visualized macroanatomic changes and contrast enhancement, which are not necessarily specific tumor characteristics and thus may not accurately differentiate tumor tissue from normal. As a result, the tumor volume is not properly conveyed on anatomic images when visual structural cues related to tumor tissue are lacking.

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Materials and methods

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Registration Framework

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arg

max

∈

{

[

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[

(

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where Tˆ T

ˆ is the estimate of the transform, and F is the family of feasible transforms.

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Scan Acquisition

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Registration Schematic

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Positron Emission Tomographic Thresholding Algorithm

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Registration Error

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Results

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Table 1

Error Values Between Threshold PET and Histology

Variable Case1 Case2 Case3 Case4 Mean ± SD Independent variables SUVmax threshold on PET (unitless) 0.6 0.6 0.6 0.6 0.6 ± 0.0 Tumor volume (cm 3 ) 12.6 9.9 7.2 6.8 9.1 ± 2.7 Dependent variables Medial axis error (mm) ∗ 14.1 7.3 8.0 1.3 7.7 ± 5.2 Boundary error (mm) ∗ 8.4 17.7 6.2 9.0 10.3 ± 5.1 Centroid error (mm) 8.1 9.0 12.2 6.9 9.1 ± 2.3 Overlap index (unitless) 0.5 0.4 0.1 0.6 0.4 ± 0.2

PET, positron emission tomography; SD, standard deviation; SUVmax, maximum standardized uptake value.

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Discussion

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Conclusion

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Validation of Automatic Target Volume Definition as Demonstrated for11 C-Choline PET/CT of Human Prostate Cancer Using Multi-modality Fusion Techniques

Rationale and Objectives

Materials and Methods

Results

Conclusions

Materials and methods

Registration Framework

Scan Acquisition

Registration Schematic

Positron Emission Tomographic Thresholding Algorithm

Registration Error

Results

Discussion

Conclusion

References

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