| 1. |
- Adjeiwaah, Mary, 1980-
(författare)
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Quality assurance for magnetic resonance imaging (MRI) in radiotherapy
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of Magnetic Resonance Imaging (MRI) in the radiotherapy (RT) treatment planning workflow is increasing. MRI offers superior soft-tissue contrast compared to Computed Tomography (CT) and therefore improves the accuracy in target volume definitions. There are, however concerns with inherent geometric distortions from system- (gradient nonlinearities and main magnetic field inhomogeneities) and patient-related sources (magnetic susceptibility effect and chemical shift). The lack of clearly defined quality assurance (QA) procedures has also raised questions on the ability of current QA protocols to detect common image quality degradations under radiotherapy settings. To fully implement and take advantage of the benefits of MRI in radiotherapy, these concerns need to be addressed.In Papers I and II, the dosimetric impact of MR distortions was investigated. Patient CTs (CT) were deformed with MR distortion vector fields (from the residual system distortions after correcting for gradient nonlinearities and patient-induced susceptibility distortions) to create distorted CT (dCT) images. Field parameters from volumetric modulated arc therapy (VMAT) treatment plans initially optimized on dCT data sets were transferred to CT data to compute new treatment plans. Data from 19 prostate and 21 head and neck patients were used for the treatment planning. The dCT and CT treatment plans were compared to determine the impact of distortions on dose distributions. No clinically relevant dose differences between distorted CT and original CT treatment plans were found. Mean dose differences were < 1.0% and < 0.5% at the planning target volume (PTV) for the head and neck, and prostate treatment plans, respectively. Strategies to reduce geometric distortions were also evaluated in Papers I and II. Using the vendor-supplied gradient non-linearity correction algorithm reduced overall distortions to less than half of the original value. A high acquisition bandwidth of 488 Hz/pixel (Paper I) and 488 Hz/mm (Paper II) kept the mean geometric distortions at the delineated structures below 1 mm. Furthermore, a patient-specific active shimming method implemented in Paper II significantly reduced the number of voxels with distortion shifts > 2 mm from 15.4% to 2.0%.B0 maps from patient-induced magnetic field inhomogeneities obtained through direct measurements and by simulations that used MR-generated synthetic CT (sCT) data were compared in Paper III. The validation showed excellent agreement between the simulated and measured B0 maps.In Paper IV, the ability of current QA methods to detect common MR image quality degradations under radiotherapy settings were investigated. By evaluating key image quality parameters, the QA protocols were found to be sensitive to some of the introduced degradations. However, image quality issues such as those caused by RF coil failures could not be adequately detected.In conclusion, this work has shown the feasibility of using MRI data for radiotherapy treatment planning as distortions resulted in a dose difference of less than 1% between distorted and undistorted images. The simulation software can be used to produce accurate B0 maps, which could then be used as the basis for the effective correction of patient-induced field inhomogeneity distortions and for the QA verification of sCT data. Furthermore, the analysis of the strengths and weaknesses in current QA tools for MRI in RT contribute to finding better methods to efficiently identify image quality errors.
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| 2. |
- Björeland, Ulrika, 1974-
(författare)
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MRI in prostate cancer : implications for target volume
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer (PCa) is the most common cancer among men, with 10 000 new cases per year in Sweden [1]. To diagnose PCa, magnetic resonance imaging (MRI) is used to identify and classify the disease. The patient’s treatment strategy depends on PCa classification and clinical data, which are weighted together into a risk group classification from 1–5. For patients with higher risk classes (>3), radiotherapy together with hormone therapy is a common treatment option [2].In radiotherapy (RT), individual treatment plans are created based on the patient’s anatomy. These plans are based on computed tomography (CT), often supplemented with MRI images. MRI and CT complement each other, as MRI has better soft tissue contrast and CT has better bone contrast. Based on the images, the volumes to be treated (target) and the volumes to be avoided (risk organs) are defined. Prostate RT is complex, and there are uncertainties regarding the patient's internal movements and how the patient is positioned before each treatment. To account for these uncertainties, the radiation field is expanded (extended margins to target) to ensure that the treatment volume receives its radiotherapy. RT is most often given in fractions. Fractionation, dose, and treatment volume depend on the patient’s risk category. The treatment area can be, for example, only prostate, prostate with extra radiation dose (boost) to an intraprostatic tumour, or prostate with lymph node (LN) irradiation. LN irradiation is most often given for preventive purposes for PCa with a risk classification >4, which means no cancer has been identified, but any microscopic spread to the LNs is being treated profylactically.In RT, target identification is essential both in the treatment planning images (CT/MRI) and at treatment. Studies have shown that PCa often re-occurs in or near the volume of the dominant (often largest) intraprostatic tumour [3, 4], and this volume is relevant for boosting. For patients treated with hormone therapy before radiotherapy, tumour identification is complicated. Hormones change the tumour characteristics, affecting the image contrast and making the tumour difficult to identify. To study this, we investigated whether texture analysis could identify the tumour volume after hormone therapy (paper II). However, even with texture analysis, the tumour was difficult to identify. A follow-up study examined whether the image information in MRI images taken before hormone therapy could indicate how the treatment fell out (paper IV). However, no correlation was seen between image features and the progression of PCa.Identifying the target and correctly positioning the patient for each treatment fraction is the most important procedure in radiotherapy. The prostate is a mobile organ; therefore, intraprostatic fiducial markers are inserted before treatment planning to reduce positioning uncertainties. Each radiotherapy session begins with an X-ray image where the markers are visible, and the radiation can be delivered based on the markers' position. The markers are also used as guidance for large target volumes, such as for prostate with LN irradiation. With better knowledge of the prostate and LN movements, the margins can potentially be reduced, followed by reduced radiation dose to healthy tissue and therefore reduced side effects for patients. Movements in the radiotherapy volume were the focus of paper I. Using MRI images, the movements of the prostate and LNs were measured during the course of radiotherapy, and we found that LN movement is independent of the movement of the prostate and that the movement varies in the target volume.In addition to the recurrence of PCa in the tumour area, there is an increased risk of recurrence in the prostate periphery close to the rectum. Since the rectum and prostate are in contact for some patients, RT must be adapted to make rectum side effects tolerable. One way to increase the distance between the prostate and the rectum is to inject a gel between the two organs. The distance makes it easier to achieve a better dose distribution to the PCa. This idea resulted in paper III, where patients were given a gel between the prostate and rectum. MRI was used to check the stability of the gel during the course of RT and was evaluated together with long-term follow-up of the patient’s well-being and acceptance of the gel. We found that the radiation dose to the rectum was lower with a spacer, although the spacer was not completely stable during treatment.
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| 3. |
- Sandgren, Kristina, 1988-
(författare)
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PET and MR imaging in prostate cancer
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The current risk assessment of prostate cancer (PC) relies on histopathological samples from biopsies and clinical variables such as prostate-specific antigen (PSA). However, this comes with uncertainties and in some cases it can be challenging to separate patients who would benefit from radical treatment and those who would not. The risk assessment tools for PC need to be improved and preferably developed into predictive markers. Medical imaging using positron emission tomography (PET) and magnetic resonance imaging (MRI) are potential diagnostic modalities for achieving such improvements. Both PET and MRI have several clinical applications in PC already and are increasingly being incorporated at different steps in the clinical management. For example, MRI is used to guide targeted biopsies, and also as a guide during planning of external beam radiotherapy treatments with focal boosting of the macroscopic visible tumour. However, more precise and individual treatment strategies demand verification of both the characterisation regarding aggressiveness and spatial distribution of the disease. To evaluate the performance of PET and MRI in detection of biochemical recurrent PC after radical prostatectomy, a systematic literature review was conducted (study I). The results of this systematic review indicated that there is a large variety of available imaging methods for PC being used for detecting local and/or locoregional recurrence. Many of the included studies were based on evaluation of patients with high PSA levels yielding high sensitivities and specificities. A pooled mean sensitivity was calculated to 84% for multiparametric MRI (mpMRI) and Choline-PET/CT. Methodological variations between and within studies were observed which limited the possibility of performing a meaningful meta-analysis. No publications evaluating radiotracers binding to prostate-specific membrane antigen (PSMA) were included in the review, although the early literature of using PSMA-PET showed much promise. To introduce a PSMA-binding radiotracer to the clinical management of PC at Umeå University Hospital a clinical trial was performed with the aim to investigate the clinical performance of the radiotracer [68Ga]PSMA-11. In this clinical trial we aimed to both evaluate the diagnostic performance and the safety of the radiotracer. To evaluate the safety, regarding radiation-exposure, absorbed organ doses as well as the effective dose were calculated in a cohort of six low-risk PC patients (study II). The results showed that the effective dose for [68Ga]PSMA-11 was 0.022 mSv/MBq, and that the kidneys and lacrimal glands were the organs receiving the highest organ doses. Based on these results, which were in line with other clinically used radiotracers, we could conclude that [68Ga]PSMA-11 is, from a radiation dosimetry perspective, a safe radiotracer to inject into patients. The diagnostic performance, specifically regarding detection of intraprostatic tumours using [68Ga]PSMA-11 (PSMA)-PET, mpMRI and [11C]Acetate (ACE)-PET was evaluated in a cohort of 55 intermediate and high-risk PC patients planned for radical prostatectomy with the whole mount histopathology as the reference test (study IV). The imaging modalities were radiologically reviewed and compared. Sensitivity regarding detection of intraprostatic lesions was calculated for each imaging modality. Regarding detection of lesions with a volume >0.5 cc and with a ISUP grade ≥2, PSMA-PET and mpMRI showed similar performance with sensitivities of 69% and 73%, respectively while ACE-PET had a sensitivity of 36%. In this clinical study, a registration procedure between histopathology and in vivo images was developed and performed in all patients. This procedure included both a 3D printed patient-specific prostate-mould, an ex vivo MRI of the specimen and image registrations (study III). The uncertainty of the precision of the registration between histopathology data and in vivo data was evaluated by comparing positions of landmarks visible in the corresponding images. The uncertainty of the method was estimated to a median in-plane error of 1.7 mm [interquartile range: 1.0, 2.5] for the entire registration procedure. To conclude, the tools for risk assessment of PC need to be improved and developed into predictive markers. When in vivo data is correlated with histopathology data, such as the data set collected within this thesis, it is possible to identify new predictive markers that can be used to improve the clinical management of PC.
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| 4. |
- Simkó, Attila, 1995-
(författare)
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Contributions to deep learning for imaging in radiotherapy
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: The increasing importance of medical imaging in cancer treatment, combined with the growing popularity of deep learning gave relevance to the presented contributions to deep learning solutions with applications in medical imaging.Relevance: The projects aim to improve the efficiency of MRI for automated tasks related to radiotherapy, building on recent advancements in the field of deep learning.Approach: Our implementations are built on recently developed deep learning methodologies, while introducing novel approaches in the main aspects of deep learning, with regards to physics-informed augmentations and network architectures, and implicit loss functions. To make future comparisons easier, we often evaluated our methods on public datasets, and made all solutions publicly available.Results: The results of the collected projects include the development of robust models for MRI bias field correction, artefact removal, contrast transfer and sCT generation. Furthermore, the projects stress the importance of reproducibility in deep learning research and offer guidelines for creating transparent and usable code repositories.Conclusions: Our results collectively build the position of deep learning in the field of medical imaging. The projects offer solutions that are both novel and aim to be highly applicable, while emphasizing generalization towards a wide variety of data and the transparency of the results.
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| 5. |
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| 6. |
- Björeland, Ulrika, et al.
(författare)
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Impact of neoadjuvant androgen deprivation therapy on magnetic resonance imaging features in prostate cancer before radiotherapy
- 2021
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Ingår i: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 17, s. 117-123
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: In locally advanced prostate cancer (PC), androgen deprivation therapy (ADT) in combination with whole prostate radiotherapy (RT) is the standard treatment. ADT affects the prostate as well as the tumour on multiparametric magnetic resonance imaging (MRI) with decreased PC conspicuity and impaired localisation of the prostate lesion. Image texture analysis has been suggested to be of aid in separating tumour from normal tissue. The aim of the study was to investigate the impact of ADT on baseline defined MRI features in prostate cancer with the goal to investigate if it might be of use in radiotherapy planning.Materials and methods: Fifty PC patients were included. Multiparametric MRI was performed before, and three months after ADT. At baseline, a tumour volume was delineated on apparent diffusion coefficient (ADC) maps with suspected tumour content and a reference volume in normal prostatic tissue. These volumes were transferred to MRIs after ADT and were analysed with first-order -and invariant Haralick -features.Results: At baseline, the median value and several of the invariant Haralick features of ADC, showed a significant difference between tumour and reference volumes. After ADT, only ADC median value could significantly differentiate the two volumes.Conclusions: Invariant Haralick -features could not distinguish between baseline MRI defined PC and normal tissue after ADT. First-order median value remained significantly different in tumour and reference volumes after ADT, but the difference was less pronounced than before ADT.
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| 7. |
- Nilsson, Erik, et al.
(författare)
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The grade of individual prostate cancer lesions predicted by magnetic resonance imaging and positron emission tomography
- 2023
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Ingår i: Communications Medicine. - : Springer Nature. - 2730-664X. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Sandgren, Kristina, et al.
(författare)
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Histopathology-validated lesion detection rates of clinically significant prostate cancer with mpMRI, [68Ga]PSMA-11-PET and [11C]Acetate-PET
- 2023
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Ingår i: Nuclear medicine communications. - : Lippincott Williams & Wilkins. - 0143-3636 .- 1473-5628. ; 44:11, s. 997-1004
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Tidskriftsartikel (refereegranskat)abstract
- Objective: PET/CT and multiparametric MRI (mpMRI) are important diagnostic tools in clinically significant prostate cancer (csPC). The aim of this study was to compare csPC detection rates with [68Ga]PSMA-11-PET (PSMA)-PET, [11C] Acetate (ACE)-PET, and mpMRI with histopathology as reference, to identify the most suitable imaging modalities for subsequent hybrid imaging. An additional aim was to compare inter-reader variability to assess reproducibility.Methods: During 2016–2019, all study participants were examined with PSMA-PET/mpMRI and ACE-PET/CT prior to radical prostatectomy. PSMA-PET, ACE-PET and mpMRI were evaluated separately by two observers, and were compared with histopathology-defined csPC. Statistical analyses included two-sided McNemar test and index of specific agreement.Results: Fifty-five study participants were included, with 130 histopathological intraprostatic lesions >0.05 cc. Of these, 32% (42/130) were classified as csPC with ISUP grade ≥2 and volume >0.5 cc. PSMA-PET and mpMRI showed no difference in performance (P = 0.48), with mean csPC detection rate of 70% (29.5/42) and 74% (31/42), respectively, while with ACE-PET the mean csPC detection rate was 37% (15.5/42). Interobserver agreement was higher with PSMA-PET compared to mpMRI [79% (26/33) vs 67% (24/38)]. Including all detected lesions from each pair of observers, the detection rate increased to 90% (38/42) with mpMRI, and 79% (33/42) with PSMA-PET.Conclusion: PSMA-PET and mpMRI showed high csPC detection rates and superior performance compared to ACE-PET. The interobserver agreement indicates higher reproducibility with PSMA-PET. The combined result of all observers in both PSMA-PET and mpMRI showed the highest detection rate, suggesting an added value of a hybrid imaging approach.
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| 9. |
- Sandgren, Kristina, et al.
(författare)
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Registration of histopathology to magnetic resonance imaging of prostate cancer
- 2021
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Ingår i: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 18, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Zarei, Maryam, et al.
(författare)
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Accuracy of gross tumour volume delineation with [68Ga]-PSMA-PET compared to histopathology for high-risk prostate cancer
- 2024
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Ingår i: Acta Oncologica. - : MJS Publishing, Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 503-510
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology.MATERIALS AND METHODS: The study population consisted of 15 patients with confirmed high-risk PC intended for prostatectomy. [68Ga]-PSMA-PET/MR was performed prior to surgery. Prostate lesions identified in histopathology were transferred to the in vivo [68Ga]-PSMA-PET/MR coordinate system. Four radiation oncologists manually delineated intraprostatic lesions based on PET data. Various semi-automatic segmentation methods were employed, including absolute and relative thresholds, adaptive threshold, and multi-level Otsu threshold.RESULTS: The gross tumour volumes (GTVs) delineated by the oncologists showed a moderate level of interobserver agreement with Dice similarity coefficient (DSC) of 0.68. In comparison with histopathology, manual delineations exhibited the highest median DSC and the lowest false discovery rate (FDR) among all approaches. Among semi-automatic approaches, GTVs generated using standardized uptake value (SUV) thresholds above 4 (SUV > 4) demonstrated the highest median DSC (0.41), with 0.51 median lesion coverage ratio, FDR of 0.66 and the 95th percentile of the Hausdorff distance (HD95%) of 8.22 mm.INTERPRETATION: Manual delineations showed a moderate level of interobserver agreement. Compared to histopathology, manual delineations and SUV > 4 exhibited the highest DSC and the lowest HD95% values. The methods that resulted in a high lesion coverage were associated with a large overestimation of the size of the lesions.
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