Quantitative analysis of breast lumpectomies using histology and micro-CT data

OBJECTIVE: Breast cancer represents a significant risk in women's health, affecting many women worldwide. Current treatment options in the U.S involve a multidisciplinary approach, most often beginning with surgery to remove cancerous tissue. Evaluation of margins for cancer on excised tissue is an important part of surgery, an important predictor of survival. As a result, there has been a great deal of research interest in intraoperative margin assessment, with a focus on fast and accurate results. Micro-computed Tomography (micro-CT) has emerged as a promising avenue to this end. We hypothesize that micro-CT scans will show a statistically significant difference in radiodensity between cancerous and non-cancerous tissue at intraoperative scan times. METHODS: 15 breast lumpectomy specimens were collected from patients undergoing surgery at Massachusetts General Hospital (MGH). Lumpectomies were scanned with a Nikon XTH225 Micro-CT scanner. Corresponding histology slides were scanned with a whole slide scanner, and matched with micro-CT scans. Representative areas of cancerous and non-cancerous tissues were segmented from micro-CT scans, and their respective radiodensity differences were tested for statistical significance. RESULTS: 9 of 15 lumpectomy cases were successfully matched with histology sections. Of the 9 cases matched, 8 showed a statistically significant difference in mean radiodensity. CONCLUSION: Due to potential confounds in the study, the results are difficult to deem conclusive. However, micro-CT remains a promising tool in margin assessment, and could be fit for clinical use with further study

Prone to supine surface-based registration for surgical planning in breast cancer treatment

Breast cancer is the most common invasive cancer in women worldwide. Many women with breast cancer have their malignant tumors detected before the lesions become clinically palpable. Occult lesions must be marked for the surgeon to ensure that they can be effectively resected. Image-guided wire localization (WGL) is the current standard of care for the excision of non-palpable carcinomas during breast conserving surgery. The integration of the information from multimodal imaging may be especially relevant in surgical planning as complement or an alternative to WGL. The combination of information from images in different positions is especially difficult due to large breast deformation. This work presents a system based on surface registration to localize the lesion in the operative position, starting from a prone MRI study and a surface of the patient in the supine positon. The pre-operative surface from the MRI is registered to the surface obtained in a supine position similar to the intraoperative setting. Triangular meshes have been used to model breast surface in both positions and surfaces are aligned using a Laplacian deformation with fiducials automatically obtained from 3 anatomical references. The evaluation of the methodology has been carried out in 13 cases in which a supine- CT was available achieving an average localization error of 6.7 m

Breast Tumor Localization by Prone to Supine Landmark Driven Registration for Surgical Planning

Breast cancer is the most common cancer in women worldwide. Screening programs and imaging improvements have increased the detection of clinically occult non-palpable lesions requiring preoperative localization. Wire guided localization (WGL) is the current standard of care for the excision of non-palpable carcinomas during breast conserving surgery. Due to the current limitations of intraoperative tumor localization approaches, the integration of multimodal imaging information may be especially relevant in surgical planning. This research proposes a novel method for performing preoperative image-to-surgical surface data alignment to determine the position of the tumor at the time of surgery and aid preoperative planning. First, the volume of the breast in the surgical position is reconstructed and a set of surface correspondences is defined. Then, the preoperative (prone) and intraoperative (supine) volumes are co-registered using landmark driven non-rigid registration methods. We compared the performances of diffeomorphic and Bspline based registration methods. Finally, our method was validated using clinical data from 67 patients considering as target registration error (TRE) the distance between the estimated tumor position and the reference surgical position. The proposed method achieved a TRE of 16.21 ± 8.18 mm and it could potentially assist the surgery planning and guidance of breast cancer treatment in the clinical practice.This work was supported in part by the Spanish Ministry of Science and Innovation under Project RTI2018-098682-B-I00 (MCIU/AEI/FEDER,UE), Project PI18/01625 (Instituto de Salud Carlos III) and Grant BGP18/00178 under Beatriz Galindo Programme; in part by the European Union's European Regional Development Fund (ERDF); and in part by the Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with Universidad Politécnica de Madrid in the line Support for Research and Development Projects for Beatriz Galindo researchers, in the context of the V Plan Regional de Investigación Científíca e Innovación Tecnológica (PRICIT)

Method for coregistration of optical measurements of breast tissue with histopathology : the importance of accounting for tissue deformations

For the validation of optical diagnostic technologies, experimental results need to be benchmarked against the gold standard. Currently, the gold standard for tissue characterization is assessment of hematoxylin and eosin (H&E)-stained sections by a pathologist. When processing tissue into H&E sections, the shape of the tissue deforms with respect to the initial shape when it was optically measured. We demonstrate the importance of accounting for these tissue deformations when correlating optical measurement with routinely acquired histopathology. We propose a method to register the tissue in the H&E sections to the optical measurements, which corrects for these tissue deformations. We compare the registered H&E sections to H&E sections that were registered with an algorithm that does not account for tissue deformations by evaluating both the shape and the composition of the tissue and using microcomputer tomography data as an independent measure. The proposed method, which did account for tissue deformations, was more accurate than the method that did not account for tissue deformations. These results emphasize the need for a registration method that accounts for tissue deformations, such as the method presented in this study, which can aid in validating optical techniques for clinical use. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License

SURGICAL NAVIGATION AND AUGMENTED REALITY FOR MARGINS CONTROL IN HEAD AND NECK CANCER

I tumori maligni del distretto testa-collo rappresentano un insieme di lesioni dalle diverse caratteristiche patologiche, epidemiologiche e prognostiche. Per una porzione considerevole di tali patologie, l’intervento chirurgico finalizzato all’asportazione completa del tumore rappresenta l’elemento chiave del trattamento, quand’anche esso includa altre modalità quali la radioterapia e la terapia sistemica. La qualità dell’atto chirurgico ablativo è pertanto essenziale al fine di garantire le massime chance di cura al paziente. Nell’ambito della chirurgia oncologica, la qualità delle ablazioni viene misurata attraverso l’analisi dello stato dei margini di resezione. Oltre a rappresentare un surrogato della qualità della resezione chirurgica, lo stato dei margini di resezione ha notevoli implicazioni da un punto di vista clinico e prognostico. Infatti, il coinvolgimento dei margini di resezione da parte della neoplasia rappresenta invariabilmente un fattore prognostico sfavorevole, oltre che implicare la necessità di intensificare i trattamenti postchirurgici (e.g., ponendo indicazione alla chemioradioterapia adiuvante), comportando una maggiore tossicità per il paziente. La proporzione di resezioni con margini positivi (i.e., coinvolti dalla neoplasia) nel distretto testa-collo è tra le più elevate in ambito di chirurgia oncologica. In tale contesto si pone l’obiettivo del dottorato di cui questa tesi riporta i risultati. Le due tecnologie di cui si è analizzata l’utilità in termini di ottimizzazione dello stato dei margini di resezione sono la navigazione chirurgica con rendering tridimensionale e la realtà aumentata basata sulla videoproiezione di immagini. Le sperimentazioni sono state svolte parzialmente presso l’Università degli Studi di Brescia, parzialmente presso l’Azienda Ospedale Università di Padova e parzialmente presso l’University Health Network (Toronto, Ontario, Canada). I risultati delle sperimentazioni incluse in questo elaborato dimostrano che l'impiego della navigazione chirurgica con rendering tridimensionale nel contesto di procedure oncologiche ablative cervico-cefaliche risulta associata ad un vantaggio significativo in termini di riduzione della frequenza di margini positivi. Al contrario, le tecniche di realtà aumentata basata sulla videoproiezione, nell'ambito della sperimentazione preclinica effettuata, non sono risultate associate a vantaggi sufficienti per poter considerare tale tecnologia per la traslazione clinica.Head and neck malignancies are an heterogeneous group of tumors. Surgery represents the mainstay of treatment for the large majority of head and neck cancers, with ablation being aimed at removing completely the tumor. Radiotherapy and systemic therapy have also a substantial role in the multidisciplinary management of head and neck cancers. The quality of surgical ablation is intimately related to margin status evaluated at a microscopic level. Indeed, margin involvement has a remarkably negative effect on prognosis of patients and mandates the escalation of postoperative treatment by adding concomitant chemotherapy to radiotherapy and accordingly increasing the toxicity of overall treatment. The rate of margin involvement in the head and neck is among the highest in the entire field of surgical oncology. In this context, the present PhD project was aimed at testing the utility of 2 technologies, namely surgical navigation with 3-dimensional rendering and pico projector-based augmented reality, in decreasing the rate of involved margins during oncologic surgical ablations in the craniofacial area. Experiments were performed in the University of Brescia, University of Padua, and University Health Network (Toronto, Ontario, Canada). The research activities completed in the context of this PhD course demonstrated that surgical navigation with 3-dimensional rendering confers a higher quality to oncologic ablations in the head and neck, irrespective of the open or endoscopic surgical technique. The benefits deriving from this implementation come with no relevant drawbacks from a logistical and practical standpoint, nor were major adverse events observed. Thus, implementation of this technology into the standard care is the logical proposed step forward. However, the genuine presence of a prognostic advantage needs longer and larger study to be formally addressed. On the other hand, pico projector-based augmented reality showed no sufficient advantages to encourage translation into the clinical setting. Although observing a clear practical advantage deriving from the projection of osteotomy lines onto the surgical field, no substantial benefits were measured when comparing this technology with surgical navigation with 3-dimensional rendering. Yet recognizing a potential value of this technology from an educational standpoint, the performance displayed in the preclinical setting in terms of surgical margins optimization is not in favor of a clinical translation with this specific aim

Calibration and Analysis of a Multimodal Micro-CT and Structured Light Imaging System for the Evaluation of Excised Breast Tissue.

A multimodal micro-computed tomography (CT) and multi-spectral structured light imaging (SLI) system is introduced and systematically analyzed to test its feasibility to aid in margin delineation during breast conserving surgery (BCS). Phantom analysis of the micro-CT yielded a signal-to-noise ratio of 34, a contrast of 1.64, and a minimum detectable resolution of 240 ?m for a 1.2?min scan. The SLI system, spanning wavelengths 490?nm to 800?nm and spatial frequencies up to 1.37 , was evaluated with aqueous tissue simulating phantoms having variations in particle size distribution, scatter density, and blood volume fraction. The reduced scattering coefficient, and phase function parameter, ?, were accurately recovered over all wavelengths independent of blood volume fractions from 0% to 4%, assuming a flat sample geometry perpendicular to the imaging plane. The resolution of the optical system was tested with a step phantom, from which the modulation transfer function was calculated yielding a maximum resolution of 3.78 cycles per mm. The three dimensional spatial co-registration between the CT and optical imaging space was tested and shown to be accurate within 0.7?mm. A freshly resected breast specimen, with lobular carcinoma, fibrocystic disease, and adipose, was imaged with the system. The micro-CT provided visualization of the tumor mass and its spiculations, and SLI yielded superficial quantification of light scattering parameters for the malignant and benign tissue types. These results appear to be the first demonstration of SLI combined with standard medical tomography for imaging excised tumor specimens. While further investigations are needed to determine and test the spectral, spatial, and CT features required to classify tissue, this study demonstrates the ability of multimodal CT/SLI to quantify, visualize, and spatially navigate breast tumor specimens, which could potentially aid in the assessment of tumor margin status during BCS

Standardized Platform for Coregistration of Noncurrent Diffuse Optical and Magnetic Resonance Breast Images Obtained in Different Geometries

We present a novel methodology for combining breast image data obtained at different times, in different geometries, and by different techniques. We combine data based on diffuse optical tomography (DOT) and magnetic resonance imaging (MRI). The software platform integrates advanced multimodal registration and segmentation algorithms, requires minimal user experience, and employs computationally efficient techniques. The resulting superposed 3-D tomographs facilitate tissue analyses based on structural and functional data derived from both modalities, and readily permit enhancement of DOT data reconstruction using MRI-derived a-priori structural information. We demonstrate the multimodal registration method using a simulated phantom, and we present initial patient studies that confirm that tumorous regions in a patient breast found by both imaging modalities exhibit significantly higher total hemoglobin concentration (THC) than surrounding normal tissues. The average THC in the tumorous regions is one to three standard deviations larger than the overall breast average THC for all patients

Breast Cancer: Modelling and Detection

This paper reviews a number of the mathematical models used in cancer modelling and then chooses a specific cancer, breast carcinoma, to illustrate how the modelling can be used in aiding detection. We then discuss mathematical models that underpin mammographic image analysis, which complements models of tumour growth and facilitates diagnosis and treatment of cancer. Mammographic images are notoriously difficult to interpret, and we give an overview of the primary image enhancement technologies that have been introduced, before focusing on a more detailed description of some of our own recent work on the use of physics-based modelling in mammography. This theoretical approach to image analysis yields a wealth of information that could be incorporated into the mathematical models, and we conclude by describing how current mathematical models might be enhanced by use of this information, and how these models in turn will help to meet some of the major challenges in cancer detection