Partial nephrectomy margin imaging using structured illumination microscopy

Wang, Mei; Tulman, David B.; Sholl, Andrew B.; Mandava, Sree Harsha; Maddox, Michael; Lee, Benjamin R.; Brown, J. Quincy

doi:10.1002/jbio.201600328

Cited by 8 publications

(7 citation statements)

References 25 publications

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“…In this future application, clinicians could utilize SIM as a tool to assess surgical margins in the operating room to identify positive margins on-site instead of waiting for the full histopathological work-up currently required. Investigation into this use would involve the combination of research our lab has done on partial nephrectomies [ 31 ] and radical prostatectomies [ 40 ] with the preliminary data and protocols presented in this work.…”

Section: Discussionmentioning

confidence: 99%

“…Ex-vivo microscopy is an emerging technology that utilizes optical-sectioning to generate histologic-analogous images of non- or minimally processed tissues at point of care and offers qualities that are promising for on-site tissue assessment in a clinical setting [ 16 , 17 ]. Some of the most popular ex-vivo microscopy techniques include confocal microscopy [ 18 – 20 ], light sheet microscopy [ 21 ], microscopy with UV-excitation (MUSE) [ 22 – 24 ], multiphoton microscopy [ 25 ], nonlinear optical imaging (NLOI) [ 26 ], optical coherence tomography/imaging (OCT) [ 27 ], and structured illumination microscopy (SIM) [ 28 – 31 ]. Many of these optical-sectioning microscopies can be combined with fluorescence markers to label specific structures such as collagen, nucleic acids, and other biomarkers.…”

Section: Introductionmentioning

confidence: 99%

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Structured illumination microscopy for cancer identification in diagnostic breast biopsies

Behr,

Alizadeh,

Buckner-Baiamonte

et al. 2024

PLoS ONE

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Breast cancer is the second most common cancer diagnosed in women in the US with almost 280,000 new cases anticipated in 2023. Currently, on-site pathology for location guidance is not available during the collection of breast biopsies or during surgical intervention procedures. This shortcoming contributes to repeat biopsy and re-excision procedures, increasing the cost and patient discomfort during the cancer management process. Both procedures could benefit from on-site feedback, but current clinical on-site evaluation techniques are not commonly used on breast tissue because they are destructive and inaccurate. Ex-vivo microscopy is an emerging field aimed at creating histology-analogous images from non- or minimally-processed tissues, and is a promising tool for addressing this pain point in clinical cancer management. We investigated the ability structured illumination microscopy (SIM) to generate images from freshly-obtained breast tissues for structure identification and cancer identification at a speed compatible with potential on-site clinical implementation. We imaged 47 biopsies from patients undergoing a guided breast biopsy procedure using a customized SIM system and a dual-color fluorescent hematoxylin & eosin (H&E) analog. These biopsies had an average size of 0.92 cm2 (minimum 0.1, maximum 4.2) and had an average imaging time of 7:29 (minimum 0:22, maximum 37:44). After imaging, breast biopsies were submitted for standard histopathological processing and review. A board-certified pathologist returned a binary diagnostic accuracy of 96% when compared to diagnoses from gold-standard histology slides, and key tissue features including stroma, vessels, ducts, and lobules were identified from the resulting images.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structured illumination microscopy for cancer identification in diagnostic breast biopsies

Behr,

Alizadeh,

Buckner-Baiamonte

et al. 2024

PLoS ONE

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“…The method for tumor margin imaging pursued by our group relies on imaging the surface of the excised tissue using an inverted epi-illumination optical sectioning microscope, specifically in our case a structured illumination microscope, described previously 10,12,15,16 . To image the irregular surface of large tumor resections such as a radical prostatectomy specimen, we leverage the compressibility of the fresh specimen under its own weight to create a flat tissue surface against a large glass slide, through which an imaging system views the tissue surface.…”

Section: Theoretical Analysismentioning

confidence: 99%

“…Our group has advanced structured illumination microscopy (SIM) for the ex vivo imaging of entire tumor surgical margins as an alternative to intensive FSA, with the goal of intra-operatively capturing gigapixel histologic panoramas of the resected tissue surface for use in the identification and correction of PSMs during the primary operation 10,11 . SIM allows for the rapid and non-destructive imaging of the circumferential margin of radical prostatectomy specimens without the time intensive embedding and cutting steps 10 .…”

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confidence: 99%

Automated gigapixel circumferential surface microscopy of the prostate

Luethy

Tulman

Brown

2020

Sci Rep

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positive surgical margins, or cancer cells found at the boundary of an excised tumor mass, are a significant problem in the management of many cancers resulting in worsened patient outcomes. The problem is exacerbated in organ sites such as the prostate, where unnecessarily wide local excisions can result in significant deterioration of post-operative quality of life due to collateral damage to neighboring structures. Yet, at the same time, incomplete tumor removal results in worsened prognosis and need for additional interventions. Here, we report the design and development of a rapid and completely automated system for intraoperative gigapixel ex vivo microscopy of the circumferential surgical prostate margin within intra-operative timeframes, called the Automated Prostate Positioning System (AppS). the AppS leverages the rotational geometry of the prostate and high speed structured illumination microscopy (SiM) to generate continuous gigapixel panoramas of the fresh intact prostate circumference, including areas of the prostate adjacent to the neurovascular bundles, the rectum, and the bladder wall. our previous work using SiM and a manual prostate handling method demonstrated the promise of the imaging technique for accurate detection of positive surgical margins. Our work here advances the technology toward clinical adoption, by demonstrating 10% greater tissue surface coverage fraction, 1.6× faster imaging throughput, and reduced number of required operator steps, compared to our prior approach. the AppS may be operated by a single person in the operating room suite within intraoperative time limits, while simultaneously delivering nearly two orders of magnitude higher tissue surface coverage than destructive and labor-intensive frozen section analysis techniques. Prostate cancer will affect over 174,000 men in the United States in 2019-31,620 of which will die-making prostate cancer the second deadliest form of the disease in males behind lung cancer 1. Several therapies exist for the treatment of prostate cancer including: external beam radiation, radioactive seed implants (brachytherapy), hormonal therapy, chemotherapy, and surgery. Surgery is a common front-line curative approach to non-metastatic cancer in many solid organs, including the prostate. Prostate cancer surgery, or radical prostatectomy, involves the total removal of the prostate gland including seminal vesicles and ductus deferens, along with surrounding tissue as needed to achieve local control of cancer spread beyond the prostate borders. The objective of successful surgery is to remove the whole prostate organ and any tumor-involved adjacent tissues, such that the prostate cancer is completely contained within the resection specimen, and no tumor cells are found at the border of the specimen. Absence of tumor cells at the inked surgical margin is called a negative surgical margin (NSM), whereas a positive surgical margin (PSM) indicates presence of tumor cells at the inked boundary of the resection specimen. Positive surgical margins are...

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“…SIM is compatible with standard fluorophores, does not require specific sample preparation and permits 3D visualization. Given all these advantages, different studies were performed to evaluate the possibility of using SIM as a rapid diagnostic tool [ 35 ], for example, with a potential shorter turnaround time than EM. Recently a 3D SIM and automated image processing have been used as a rapid diagnostic tool of foot process effacement using routine paraffin sections from biopsies of patients with minimal change disease [ 36 ] ( Figure 3B and C ).…”

Section: Pushing Resolution Beyond Limits: Super-resolution Imaging Omentioning

confidence: 99%

Imaging the kidney: from light to super-resolution microscopy

Angelotti¹,

Antonelli²,

Conte³

et al. 2019

Nephrology Dialysis Transplantation

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The important achievements in kidney physiological and pathophysiological mechanisms can largely be ascribed to progress in the technology of microscopy. Much of what we know about the architecture of the kidney is based on the fundamental descriptions of anatomic microscopists using light microscopy and later by ultrastructural analysis provided by electron microscopy. These two techniques were used for the first classification systems of kidney diseases and for their constant updates. More recently, a series of novel imaging techniques added the analysis in further dimensions of time and space. Confocal microscopy allowed us to sequentially visualize optical sections along the z-axis and the availability of specific analysis software provided a three-dimensional rendering of thicker tissue specimens. Multiphoton microscopy permitted us to simultaneously investigate kidney function and structure in real time. Fluorescence-lifetime imaging microscopy allowed to study the spatial distribution of metabolites. Super-resolution microscopy increased sensitivity and resolution up to nanoscale levels. With cryo-electron microscopy, researchers could visualize the individual biomolecules at atomic levels directly in the tissues and understand their interaction at subcellular levels. Finally, matrix-assisted laser desorption/ionization imaging mass spectrometry permitted the measuring of hundreds of different molecules at the same time on tissue sections at high resolution. This review provides an overview of available kidney imaging strategies, with a focus on the possible impact of the most recent technical improvements.

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Partial nephrectomy margin imaging using structured illumination microscopy

Cited by 8 publications

References 25 publications

Structured illumination microscopy for cancer identification in diagnostic breast biopsies

Structured illumination microscopy for cancer identification in diagnostic breast biopsies

Automated gigapixel circumferential surface microscopy of the prostate

Imaging the kidney: from light to super-resolution microscopy

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