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Optimization in radiotherapy: correlation between imaging and histopathology in prostate cancer
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.ORCID iD: 0000-0001-8747-4759
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Medical imaging is increasingly used to inform on the clinical decision-making in prostate cancer (PCa). However, the ways in which tumour pathology is reflected in imaging remains poorly understood. The aim of this thesis was to provide insights into the associations between image characteristics and histopathological features that can be leveraged for improving radiotherapy. 

Methods: A pipeline of registration algorithms were developed to align a gold standard histopathological reference and in vivo imaging. We investigated the ability of image summary measures to discriminate between histological grades of PCa, and examined how detectability varied across lesions characterized by grades and by combined markers of cellular proliferation and differentiation. Finally, we conducted an in silico evaluation of a radiotherapy treatment protocol, based on the ongoing HYPO-RT-PC-boost phase II trial (NCT06220435). 

Results: The registration pipeline provided the means to investigate associations between imaging characteristics and histopathological features. We demonstrated that image measures derived from in vivo imaging can distinguish between lower- and higher-grade PCa, using partially discriminative cut-off values. Further, we showed that many detected lesions were both high-grade and had a higher-risk profile, characterized by high proliferation and low differentiation. Undetected lesions were more often lower-grade, but did not predominantly exhibit the low-risk combination of low proliferation and high differentiation. Furthermore, we showed that image summary measures can distinguish between higher- and lower-risk lesions, suggesting further prognostic potential of the imaging modalities. By incorporating multiple observer delineations of the visible tumour, the results of the in silico evaluation indicate that radiation oncologists delineate different tumour volumes, but they could all still obtain good coverage in sites containing more aggressive disease. These results provide a rationale for prioritizing sensitive structures during treatment planning.

Conclusion: Medical imaging modalities hold untapped potential to inform the clinical decision making. However, the inability to identify tumour on medical imaging does not necessarily translate to inadequate dose coverage in radiotherapy. The inherent complexity of generating large-scale datasets with co-registered imaging and histopathology limits generalizability and underscores the importance of interstudy harmonization in imaging protocols and histopathological evaluation.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2025. , p. 71
Publication channel
978-91-8070-755-8
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2375
Keywords [en]
prostate cancer, PET, PSMA, mpMRI, imaging, histopathology, hypofractionation, boost
National Category
Radiology and Medical Imaging Cancer and Oncology Medical Imaging
Identifiers
URN: urn:nbn:se:umu:diva-243190ISBN: 978-91-8070-755-8 (electronic)ISBN: 978-91-8070-754-1 (print)OAI: oai:DiVA.org:umu-243190DiVA, id: diva2:1991624
Public defence
2025-09-26, Stora hörsalen 5B, plan 6, 09:00 (English)
Opponent
Supervisors
Available from: 2025-09-05 Created: 2025-08-25 Last updated: 2025-08-25Bibliographically approved
List of papers
1. Registration of histopathology to magnetic resonance imaging of prostate cancer
Open this publication in new window or tab >>Registration of histopathology to magnetic resonance imaging of prostate cancer
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2021 (English)In: Physics and Imaging in Radiation Oncology, E-ISSN 2405-6316, Vol. 18, p. 19-25Article in journal (Refereed) Published
Abstract [en]

Background and purpose: The diagnostic accuracy of new imaging techniques requires validation, preferably by histopathological verification. The aim of this study was to develop and present a registration procedure between histopathology and in-vivo magnetic resonance imaging (MRI) of the prostate, to estimate its uncertainty and to evaluate the benefit of adding a contour-correcting registration.

Materials and methods: For twenty-five prostate cancer patients, planned for radical prostatectomy, a 3D-printed prostate mold based on in-vivo MRI was created and an ex-vivo MRI of the specimen, placed inside the mold, was performed. Each histopathology slice was registered to its corresponding ex-vivo MRI slice using a 2D-affine registration. The ex-vivo MRI was rigidly registered to the in-vivo MRI and the resulting transform was applied to the histopathology stack. A 2D deformable registration was used to correct for specimen distortion concerning the specimen's fit inside the mold. We estimated the spatial uncertainty by comparing positions of landmarks in the in-vivo MRI and the corresponding registered histopathology stack.

Results: Eighty-four landmarks were identified, located in the urethra (62%), prostatic cysts (33%), and the ejaculatory ducts (5%). The median number of landmarks was 3 per patient. We showed a median in-plane error of 1.8 mm before and 1.7 mm after the contour-correcting deformable registration. In patients with extraprostatic margins, the median in-plane error improved from 2.1 mm to 1.8 mm after the contour-correcting deformable registration.

Conclusions: Our registration procedure accurately registers histopathology to in-vivo MRI, with low uncertainty. The contour-correcting registration was beneficial in patients with extraprostatic surgical margins.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
Histopathology correlation, Image registration, PET/MRI, Prostate cancer
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-182584 (URN)10.1016/j.phro.2021.03.004 (DOI)000662270600004 ()2-s2.0-85104070374 (Scopus ID)
Available from: 2021-04-29 Created: 2021-04-29 Last updated: 2025-08-25Bibliographically approved
2. The grade of individual prostate cancer lesions predicted by magnetic resonance imaging and positron emission tomography
Open this publication in new window or tab >>The grade of individual prostate cancer lesions predicted by magnetic resonance imaging and positron emission tomography
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2023 (English)In: Communications Medicine, E-ISSN 2730-664X, Vol. 3, no 1, article id 164Article in journal (Refereed) Published
Abstract [en]

Background: Multiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET) are widely used for the management of prostate cancer (PCa). However, how these modalities complement each other in PCa risk stratification is still largely unknown. We aim to provide insights into the potential of mpMRI and PET for PCa risk stratification.

Methods: We analyzed data from 55 consecutive patients with elevated prostate-specific antigen and biopsy-proven PCa enrolled in a prospective study between December 2016 and December 2019. [68Ga]PSMA-11 PET (PSMA-PET), [11C]Acetate PET (Acetate-PET) and mpMRI were co-registered with whole-mount histopathology. Lower- and higher-grade lesions were defined by International Society of Urological Pathology (ISUP) grade groups (IGG). We used PET and mpMRI data to differentiate between grades in two cases: IGG 3 vs. IGG 2 (case 1) and IGG ≥ 3 vs. IGG ≤ 2 (case 2). The performance was evaluated by receiver operating characteristic (ROC) analysis.

Results: We find that the maximum standardized uptake value (SUVmax) for PSMA-PET achieves the highest area under the ROC curve (AUC), with AUCs of 0.72 (case 1) and 0.79 (case 2). Combining the volume transfer constant, apparent diffusion coefficient and T2-weighted images (each normalized to non-malignant prostatic tissue) results in AUCs of 0.70 (case 1) and 0.70 (case 2). Adding PSMA-SUVmax increases the AUCs by 0.09 (p < 0.01) and 0.12 (p < 0.01), respectively.

Conclusions: By co-registering whole-mount histopathology and in-vivo imaging we show that mpMRI and PET can distinguish between lower- and higher-grade prostate cancer, using partially discriminative cut-off values.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-224145 (URN)10.1038/s43856-023-00394-7 (DOI)001103117100002 ()37945817 (PubMedID)
Funder
Swedish Cancer Society, 21 1594 Pj
Available from: 2024-05-08 Created: 2024-05-08 Last updated: 2025-08-25Bibliographically approved
3. Detection of intraprostatic lesions using multiparametric MRI, 68Ga-PSMA-PET and 68Ga-PSMA-PET/MRI:: associations with tissue prostate-specific antigen and Ki-67 expression
Open this publication in new window or tab >>Detection of intraprostatic lesions using multiparametric MRI, 68Ga-PSMA-PET and 68Ga-PSMA-PET/MRI:: associations with tissue prostate-specific antigen and Ki-67 expression
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(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-243188 (URN)
Available from: 2025-08-19 Created: 2025-08-19 Last updated: 2025-08-25Bibliographically approved
4. Ultra-hypofractionated radiotherapy with focal boost for high-risk localized prostate cancer (HYPO-RT-PC-boost): In silico evaluation with histological reference
Open this publication in new window or tab >>Ultra-hypofractionated radiotherapy with focal boost for high-risk localized prostate cancer (HYPO-RT-PC-boost): In silico evaluation with histological reference
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(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-243189 (URN)
Available from: 2025-08-19 Created: 2025-08-19 Last updated: 2025-08-25Bibliographically approved

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