Tissue clearing and 3D reconstruction of digitized, serially sectioned slides provide novel insights into pancreatic cancer

Kiemen, Ashley; Damanakis, Alexander; Braxton, Alicia M.; He, Jin; Laheru, Daniel A.; Fishman, Elliot K.; Chames, Patrick; Pérez, Cristina Almagro; Wu, Pei‐Hsun; Wirtz, Denis; Wood, Laura D.; Hruban, Ralph H.

doi:10.1016/j.medj.2022.11.009

Cited by 17 publications

(24 citation statements)

References 107 publications

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“…One important and open question concerns the use of 3D histology in clinical settings. Indeed, this technology offers unprecedented opportunities for improved diagnosis [ 1 , 2 ]. However, some improvements are still needed.…”

Section: Discussionmentioning

confidence: 99%

“…Histological analysis of all tissues is highly relevant both in the clinical setting, enabling more accurate and robust diagnosis [ 1 , 2 ], and in basic and preclinical research [ 3 ]. This kind of staining which mimics classical H&E coupled with several clearing and imaging techniques has the advantage, compared with antibodies, of being inexpensive and suitable for several tissue types.…”

Section: Discussionmentioning

confidence: 99%

“…Three-dimensional (3D) reconstruction at cellular or sub-cellular resolutions of intact biological specimens could offer several advantages in both clinical and pre-clinical studies, for example, in cancer diagnosis, by helping to accurately determine the disease stage [ 1 ], as recently reported [ 2 ], or to study anatomical alterations with cell-type specificity on whole animal organs after the application of specific stimuli or treatments [ 3 ]. Using classical histological techniques, such as hematoxylin and eosin (H&E) staining and immunohistochemistry, tissues need to be fixed or frozen, sectioned, mounted, and then stained before being acquired.…”

Section: Introductionmentioning

confidence: 99%

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A Guide to Perform 3D Histology of Biological Tissues with Fluorescence Microscopy

Laurino

Franceschini

Pesce

et al. 2023

IJMS

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The analysis of histological alterations in all types of tissue is of primary importance in pathology for highly accurate and robust diagnosis. Recent advances in tissue clearing and fluorescence microscopy made the study of the anatomy of biological tissue possible in three dimensions. The combination of these techniques with classical hematoxylin and eosin (H&E) staining has led to the birth of three-dimensional (3D) histology. Here, we present an overview of the state-of-the-art methods, highlighting the optimal combinations of different clearing methods and advanced fluorescence microscopy techniques for the investigation of all types of biological tissues. We employed fluorescence nuclear and eosin Y staining that enabled us to obtain hematoxylin and eosin pseudo-coloring comparable with the gold standard H&E analysis. The computational reconstructions obtained with 3D optical imaging can be analyzed by a pathologist without any specific training in volumetric microscopy, paving the way for new biomedical applications in clinical pathology.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Guide to Perform 3D Histology of Biological Tissues with Fluorescence Microscopy

Laurino

Franceschini

Pesce

et al. 2023

IJMS

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“…[6,7] Obtaining accurate, 3D views of microanatomical structures is important for improving our understanding of the early stages of pancreatic cancer development. [5,[7][8][9] Existing workflows utilize medical images derived from CT, X-ray, MRI, and EUS to 3D print anatomical models of human tissues and have proven to be scientifically and clinically useful. [10][11][12] 3D printing allows scaling-up of microscopic structures to sizes discernable by the naked eye and scaling-down of excessively large structures to similarly manageable scales.…”

Section: Introductionmentioning

confidence: 99%

“…[20] CODA has revealed striking heterogeneity in the incidence, morphology, and molecular characteristics of PanINs and insights into the 3D nature of PDAC invasion into the adjacent pancreatic parenchyma. [8,[20][21][22][23][24][25] However, the power of CODA in creating accurate, digital 3D reconstructions of tissue is limited by the 2D nature of computer screens-3D anatomical renderings are visualized as 2D images or rotating videos (Video S1, Supporting Information). Here, we present an extension to the CODA technique through which normal pancreatic ducts, PanINs, and PDACs may be accurately 3D printed.…”

Section: Introductionmentioning

confidence: 99%

High‐Resolution 3D Printing of Pancreatic Ductal Microanatomy Enabled by Serial Histology

Kiemen,

Forjaz,

Sousa

et al. 2024

Adv Materials Technologies

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Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that can develop from pancreatic intraepithelial neoplasia (PanIN), a microscopic lesion in the pancreatic ductal system. PanIN and PDAC are conventionally studied in 2D via histological tissue sections. As such, their true structure is poorly understood due to the inability to image them in 3D. CODA, a recently developed technique for reconstruction of tissues at cellular resolution, is used to study the 3D morphology of the pancreas. Here, CODA is extended through 3D printing of normal pancreatic ducts, PanIN, and PDAC at cm‐scale and µm resolution. A methodology is presented to create 3D printable files from anatomical maps generated from serial histological images and to show detailed validation of the accuracy of this method. Existing 3D printing workflows utilizing medical images derived from computerized tomography (CT), X‐ray, and magnetic resonance imaging (MRI) are scientifically proven to be useful in printing whole organ‐scale structures with sub‐mm resolution. Here, using serial histological sections, it is demonstrated that 3D printing of higher‐resolution structures is also possible. Finally, with the 3D models of normal ducts, PanIN, and PDAC, marked changes to the structure of the human pancreas during tumorigenesis are revealed.

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Obesity‐ and diet‐induced plasticity in systems that control eating and energy balance

Ferrario,

Münzberg‐Gruening,

Rinaman

et al. 2024

Obesity

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In April 2023, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in partnership with the National Institute of Child Health and Human Development, the National Institute on Aging, and the Office of Behavioral and Social Sciences Research, hosted a 2‐day online workshop to discuss neural plasticity in energy homeostasis and obesity. The goal was to provide a broad view of current knowledge while identifying research questions and challenges regarding neural systems that control food intake and energy balance. This review includes highlights from the meeting and is intended both to introduce unfamiliar audiences with concepts central to energy homeostasis, feeding, and obesity and to highlight up‐and‐coming research in these areas that may be of special interest to those with a background in these fields. The overarching theme of this review addresses plasticity within the central and peripheral nervous systems that regulates and influences eating, emphasizing distinctions between healthy and disease states. This is by no means a comprehensive review because this is a broad and rapidly developing area. However, we have pointed out relevant reviews and primary articles throughout, as well as gaps in current understanding and opportunities for developments in the field.

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Tissue clearing and 3D reconstruction of digitized, serially sectioned slides provide novel insights into pancreatic cancer

Cited by 17 publications

References 107 publications

A Guide to Perform 3D Histology of Biological Tissues with Fluorescence Microscopy

A Guide to Perform 3D Histology of Biological Tissues with Fluorescence Microscopy

High‐Resolution 3D Printing of Pancreatic Ductal Microanatomy Enabled by Serial Histology

Obesity‐ and diet‐induced plasticity in systems that control eating and energy balance

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