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Development and Clinical Evaluation of New Approaches in Breast Cancer Diagnosis: Differential Phase Contrast Mammography


Hauser, Nik. Development and Clinical Evaluation of New Approaches in Breast Cancer Diagnosis: Differential Phase Contrast Mammography. 2013, University of Zurich, Faculty of Medicine.

Abstract

Purpose, Objectives
Differential phase contrast and scattering-based X-ray mammography is known to provide additional and complementary diagnostic information and may provide additional and complementary clinically relevant information compared with absorption-based mammography. This new diagnostic technology has the potential to play a crucial role in medical diagnostics. The preliminary results presented report on the first mammographic investigation of five native, i.e. - freshly dissected, breasts carried out with a grating interferometer and a conventional X-ray tube source. Four patients in this initial study had histopathologically-proven invasive breast cancer. One male patient, without the presence of any malignant formations within the resected breast, was included as a control specimen.
Another investigation evaluated the method of differential phase contrast mammography to distinguish between benign and malignant microcalcifications with the benefit to increase accuracy of early breast cancer diagnosis. Two major types of microcalcifications may be distinguished within breast tissue. Type I microcalcifications consist of calcium oxalate dehydrate whereas type II microcalcifications are composed of calcium phosphates. Type I may most frequently be seen in benign lesions whereas type II may be indicative for proliferative lesions, including invasive carcinoma. The goal of this study is to distinguish the two types of microcalcifications by the use of a non-invasive approach.
After these first evaluations of the mammographic investigation, in an additional step the new technology has been evaluated with regard to image quality and clinical relevance by the use of two blinded international multicenter reader studies.

Patients and Methods
We used a Talbot-Lau grating setup installed on a conventional, low-brilliance X-ray source: the interferometer operated at the 5th Talbot distance, at a tube voltage of 40 kVp with mean energy of 28 keV and at a current of 25 mA. The device simultaneously recorded absorption, differential phase and small-angle scattering signals from the native breast tissue. These quantities were then combined into novel color- and high-frequency-enhanced radiographic images. Pre-surgical images (conventional mammography, ultrasonography and magnetic resonance imaging (MRI)) supported the findings and clinical relevance was verified.
Based on these results, indicating clinical relevance, we investigated non-fixed mastectomy samples of 33 patients with invasive breast cancer, using the described grating-based differential phase contrast mammography (mammoDPC) device. We simultaneously recorded absorption, differential phase contrast, and small-angle scattering signals that were combined into high-frequency-enhanced images with a dedicated image fusion algorithm. Six international, expert breast radiologists evaluated clinical digital and experimental mammograms in a two-part blinded reader study. The results were statistically analyzed in terms of image quality and clinical relevance.

Results
The first approach yielded complementary and otherwise inaccessible information on the electron density distribution and the small-angle scattering power of the breast samples at the microscopic scale. This information can be transferred into imaging improvement and may be used to address clinically-relevant, yet unresolved questions such as: unequivocally discerning between malignant and pre-malignant changes and post-operative scars and distinguishing cancer-invaded regions within healthy tissue.
First unpublished results presented here of phase contrast mammography indicate that this technique implies the potential to distinguish between different types of microcalcifications and therefore may serve as a crucial step forward to improve early breast cancer diagnosis.
On the basis of the presented results, the comparison of mammoDPC with clinical digital mammography by the blinded reader studies revealed the general quality of the images to be significantly superior (p<0.001), sharpness and lesion delineation as well as general visibility of calcifications to be significantly more assessable (p<0.001) and delineation of surface structures to be significantly sharper (p<0.001). Spiculations were significantly better identified by the readers and the overall clinically relevant information provided by mammoDPC was judged to be superior (p<0.001).

Conclusions
With the approaches described to investigate native breast tissue samples by the use of the differential phase contrast mammography the first and unique ex-vivo images of fresh, native breast tissue could be obtained from mastectomy specimens using grating interferometry. By the use of fusion algorithms, we demonstrate that fused images of absorption, phase contrast and scattering signals acquired with mammoDPC have the potential to deliver enhanced digital mammography.
This technique allows to distinguish between different types of microcalcifications within breast tissue and therefore may serve as a new non-invasive tool in early breast cancer diagnosis.
The complementary information gained by this technique yielded clinical images of generally superior quality and has the potential to lead to improved radiological breast diagnostics. The promising presented results advanced us toward the ultimate goal: using grating interferometry in-vivo on humans in a clinical setting.

Abstract

Purpose, Objectives
Differential phase contrast and scattering-based X-ray mammography is known to provide additional and complementary diagnostic information and may provide additional and complementary clinically relevant information compared with absorption-based mammography. This new diagnostic technology has the potential to play a crucial role in medical diagnostics. The preliminary results presented report on the first mammographic investigation of five native, i.e. - freshly dissected, breasts carried out with a grating interferometer and a conventional X-ray tube source. Four patients in this initial study had histopathologically-proven invasive breast cancer. One male patient, without the presence of any malignant formations within the resected breast, was included as a control specimen.
Another investigation evaluated the method of differential phase contrast mammography to distinguish between benign and malignant microcalcifications with the benefit to increase accuracy of early breast cancer diagnosis. Two major types of microcalcifications may be distinguished within breast tissue. Type I microcalcifications consist of calcium oxalate dehydrate whereas type II microcalcifications are composed of calcium phosphates. Type I may most frequently be seen in benign lesions whereas type II may be indicative for proliferative lesions, including invasive carcinoma. The goal of this study is to distinguish the two types of microcalcifications by the use of a non-invasive approach.
After these first evaluations of the mammographic investigation, in an additional step the new technology has been evaluated with regard to image quality and clinical relevance by the use of two blinded international multicenter reader studies.

Patients and Methods
We used a Talbot-Lau grating setup installed on a conventional, low-brilliance X-ray source: the interferometer operated at the 5th Talbot distance, at a tube voltage of 40 kVp with mean energy of 28 keV and at a current of 25 mA. The device simultaneously recorded absorption, differential phase and small-angle scattering signals from the native breast tissue. These quantities were then combined into novel color- and high-frequency-enhanced radiographic images. Pre-surgical images (conventional mammography, ultrasonography and magnetic resonance imaging (MRI)) supported the findings and clinical relevance was verified.
Based on these results, indicating clinical relevance, we investigated non-fixed mastectomy samples of 33 patients with invasive breast cancer, using the described grating-based differential phase contrast mammography (mammoDPC) device. We simultaneously recorded absorption, differential phase contrast, and small-angle scattering signals that were combined into high-frequency-enhanced images with a dedicated image fusion algorithm. Six international, expert breast radiologists evaluated clinical digital and experimental mammograms in a two-part blinded reader study. The results were statistically analyzed in terms of image quality and clinical relevance.

Results
The first approach yielded complementary and otherwise inaccessible information on the electron density distribution and the small-angle scattering power of the breast samples at the microscopic scale. This information can be transferred into imaging improvement and may be used to address clinically-relevant, yet unresolved questions such as: unequivocally discerning between malignant and pre-malignant changes and post-operative scars and distinguishing cancer-invaded regions within healthy tissue.
First unpublished results presented here of phase contrast mammography indicate that this technique implies the potential to distinguish between different types of microcalcifications and therefore may serve as a crucial step forward to improve early breast cancer diagnosis.
On the basis of the presented results, the comparison of mammoDPC with clinical digital mammography by the blinded reader studies revealed the general quality of the images to be significantly superior (p<0.001), sharpness and lesion delineation as well as general visibility of calcifications to be significantly more assessable (p<0.001) and delineation of surface structures to be significantly sharper (p<0.001). Spiculations were significantly better identified by the readers and the overall clinically relevant information provided by mammoDPC was judged to be superior (p<0.001).

Conclusions
With the approaches described to investigate native breast tissue samples by the use of the differential phase contrast mammography the first and unique ex-vivo images of fresh, native breast tissue could be obtained from mastectomy specimens using grating interferometry. By the use of fusion algorithms, we demonstrate that fused images of absorption, phase contrast and scattering signals acquired with mammoDPC have the potential to deliver enhanced digital mammography.
This technique allows to distinguish between different types of microcalcifications within breast tissue and therefore may serve as a new non-invasive tool in early breast cancer diagnosis.
The complementary information gained by this technique yielded clinical images of generally superior quality and has the potential to lead to improved radiological breast diagnostics. The promising presented results advanced us toward the ultimate goal: using grating interferometry in-vivo on humans in a clinical setting.

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Additional indexing

Item Type:Habilitation
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gynecology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:April 2013
Deposited On:03 Mar 2015 14:18
Last Modified:08 Dec 2017 12:27

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