Publications
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Aalborg, Christian; Schjelderup, Patrick; Negård, Anne; Dam-Jensen, Jens Kristian; Dam-Dalgeir, Gertrud & Leland-Try, Marte
[Show all 8 contributors for this article]
(2026).
Intra- and interobserver variability in renal multiparametric magnetic resonance imaging: T1 mapping, diffusion-weighted imaging, arterial spin labeling, blood oxygen level-dependent and renal artery flow measurements utilizing manual segmentation.
Quantitative Imaging in Medicine and Surgery (QIMS).
ISSN 2223-4292.
16(7),
p. 1–14.
doi:
10.21037/qims-2025-1-2685.
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Meltzer, Sebastian; Landmark, Silje Sjåvik; Benth, Jurate Saltyte; Negård, Anne; Hamre, Hanne Mari & Kersten, Christian
[Show all 11 contributors for this article]
(2026).
Carcinoembryonic Antigen Flare Under Oxaliplatin-Based Chemotherapy Predicts Benefit from Nivolumab in Metastatic Microsatellite-Stable Colorectal Cancer–A Post Hoc Analysis of METIMMOX Trial Data.
ImmunoTargets and Therapy.
15.
doi:
10.2147/ITT.S594176.
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Background: The randomized METIMMOX trial evaluated short-course oxaliplatin-based chemotherapy alternating with the immune checkpoint inhibitor nivolumab in patients with previously untreated, unresectable abdominal metastases from microsatellite-stable/mismatch repair-proficient colorectal cancer. A subgroup receiving this experimental treatment showed remarkably improved outcome compared to control arm patients who received chemotherapy alone and had median progression-free survival (PFS) of 9.3 months. We examined whether the kinetics of serum carcinoembryonic antigen (CEA) could provide insights into responsiveness to the METIMMOX regimen.
Methods: Patients were randomly assigned to the control arm (oxaliplatin with bolus 5-fluorouracil/folinic acid, Q2W) or the experimental arm (alternating two cycles of chemotherapy Q2W and nivolumab Q2W). In this post hoc biomarker analysis, CEA levels were measured at baseline, at each treatment administration, and every two months during prespecified treatment breaks. Patients were categorized according to CEA kinetics—Flare (transient ≥ 20% increase above baseline), Non-responding (gradual increase), and Stable/Responding (values around baseline or gradually decreasing).
Results: Flare comprised 16 out of 71 patients. According to Log rank test, experimental-arm Flare (n = 6) had significantly improved PFS (median 34.9 months) compared to Stable/Responding (n = 21; median PFS 9.9 months; p = 0.005) and Non-responding (n = 9; median PFS 2.1 months; p = 0.007). Flare was not associated with improved PFS for control-arm subjects. Adjusted Cox regression analysis indicated that experimental-arm Flare exhibited a lower progression risk than Non-responding for up to 6.2 months, creating an observation period for a potential decrease following the initial increase.
Conclusion: CEA-Flare may indicate immune checkpoint inhibitor responsiveness following short-course oxaliplatin-based chemotherapy in this patient population; however, this is an exploratory finding that requires prospective validation.
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Borgbjerg, Jens; Breen, Bendik Stensby; Kristiansen, Cathrine Helgestad; Larsen, Nis Elbrønd; Medrud, Lise & Mikalone, Rasa
[Show all 12 contributors for this article]
(2025).
Agreement between Routine-Dose and Lower-Dose CT with and without Deep Learning–based Denoising for Active Surveillance of Solid Small Renal Masses: A Multiobserver Study.
Radiology: Imaging Cancer.
7(4).
doi:
10.1148/rycan.240250.
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Interobserver agreement for CT-based assessment of small renal masses during active surveillance was similar between routine-dose and lower-dose images acquired using iterative reconstruction, and deep learning–based denoising enabled dose reduction to submillisievert levels.
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Hundvin, Johanna Austrheim; Bornstein, Marius; Negård, Anne; Holmedal, Stein Harald; Meltzer, Sebastian & Ree, Anne Hansen
[Show all 8 contributors for this article]
(2025).
Low b-values in apparent diffusion coefficient calculations overestimate diffusion in rectal cancer.
Acta Oncologica.
ISSN 0284-186X.
64,
p. 1430–1436.
doi:
10.2340/1651-226x.2025.44028.
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Background and purpose: The apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI (DWI), is commonly calculated using a monoexponential model. However, there is no consensus on optimal b-value selection for ADC quantification in rectal cancer. This prospective observational study evaluated how varying b-value combinations influence ADC values.
Patient/material and methods: DWI with seven b-values (b = 0, 25, 50, 100, 500, 1,000, and 1,300 s/mm2) was acquired from 23 rectal cancer patients in the OxyTarget study (NCT01816607) using a 1.5T Philips Achieva scanner. Two radiologists independently delineated whole-tumour volumes of interest. ADC values were calculated using 18 different b-value combinations and compared with a biexponential reference.
Results: Tumour ADCs varied significantly across b-value combinations. Excluding low b-values (b ≤ 100 s/mm²) led to reduced ADCs. Although b = 0 s/mm² is commonly included in ADC calculations, this study demonstrates that its inclusion leads to substantial overestimation. The use of two or three b-values from b = 500, 1,000, and 1,300 s/mm² yielded the smallest deviations from the biexponential reference.
Interpretation: In rectal cancer, tumour ADC calculated using the monoexponential model is strongly influenced by the choice of b-values. By eliminating the contribution from perfusion (b ≤ 100 s/mm2) the uncertainty in the calculations is significantly reduced. Our findings support the use of b-values exceeding 100 s/mm², ideally in combination with a high b-value of at least 1,000 s/mm², when assessing diffusion using the monoexponential model. Consistent b-value combinations across studies are recommended for reliable quantitative comparisons of ADC values.
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Bakke, Kine Mari; Bjørnetrø, Tonje; Bousquet, Paula; Sanabria-Moreno, Adriana Maria; Meltzer, Sebastian & Lüders, Torben
[Show all 15 contributors for this article]
(2025).
Dissemination of Mitochondrial DNA Variants: Looking at the ‘Bigger’ Picture of the Tumour Microenvironment in Rectal Cancer Patients.
Journal of Extracellular Biology (J Ex Bio).
4(11).
doi:
10.1002/jex2.70097.
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ABSTRACT The tumour microenvironment (TME) constitution is decisive for cancer outcome and is manifested in diffusion‐weighted (DW) magnetic resonance imaging (MRI). We hypothesized that the TME metabolic state is reflected by mitochondrial DNA (mtDNA) secreted in extracellular vesicles (EVs) and examined whether plasma EV‐mtDNA variants may divulge MRI‐assessed TME attributes of rectal cancer aggressiveness. On the diagnostic MRI scans from 60 rectal cancer patients, the apparent diffusion coefficient (ADC) was calculated on DW images ( n = 29), and tumour volume ( n = 57) and extramural vascular invasion (EMVI; all patients) were determined on anatomical images. Plasma EVs (all patients) were isolated by size exclusion chromatography and verified for EV features. The EV‐mtDNA was sequenced along with mtDNA in whole blood (WB; normal tissue) to calculate the EV/WB‐mtDNA total variant number (TVN) and heteroplasmic variant number (HVN)—as a proxy for TME intracellular mtDNA variants expelled in EVs. Low EV/WB‐mtDNA TVN and HVN, indicative of hampered clearance of mutated mtDNA via EVs, were associated with low ADC (high TME cell density; p = 0.018, p = 0.005) and a large tumour volume ( p = 0.002, p = 0.003). Likewise, low EV/WB‐mtDNA TVN and HVN were associated with positive EMVI (tumour infiltration in blood vessels; p = 0.002, p = 0.003) and histologic ypN stage 1–2 (lymph nodes with tumour cells surviving radiotherapy; p = 0.002, p = 0.005), both indicators of high tumour aggressiveness. High cellular density may hamper the clearance of pathogenic tumour mtDNA variants by EVs and thus promote rectal cancer aggressiveness. Trial Registration : ClinicalTrials.gov: NCT01816607. Registered 22 March 2013, https://clinicaltrials.gov/ct2/show/NCT01816607
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Viktil, Ellen; Hanekamp, Bettina; Nesbakken, Arild; Løberg, Else Marit; Sjo, Ole Helmer & Negård, Anne
[Show all 8 contributors for this article]
(2024).
Early rectal cancer: The diagnostic performance of MRI supplemented with a rectal micro-enema and a modified staging system to identify tumors eligible for local excision.
Acta Radiologica Open.
13(5).
doi:
10.1177/20584601241241523.
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Background In staging early rectal cancers (ERC), submucosal tumor depth is one of the most important features determining the possibility of local excision (LE). The micro-enema (Bisacodyl) induces submucosal edema and may hypothetically improve the visualization of tumor depth. Purpose To test the diagnostic performance of MRI to identify ERC suitable for LE when adding a pre-procedural micro-enema and concurrent use of a modified classification system. Material and Methods In this prospective study, we consecutively included 73 patients with newly diagnosed rectal tumors. Two experienced radiologists independently interpreted the MRI examinations, and diagnostic performance was calculated for local tumors eligible for LE (Tis-T1sm2, n = 43) and non-local tumors too advanced for LE (T1sm3-T3b, n = 30). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were registered for each reader. Inter- and intra-reader agreements were assessed by kappa statistics. Lymph node status was derived from the clinical MRI reports. Results Reader1/reader2 achieved sensitivities of 93%/86%, specificities of 90%/83%, PPV of 93%/88%, and NPV of 90%/81%, respectively, for identifying tumors eligible for LE. Rates of overstaging of local tumors were 7% and 14% for the two readers, and kappa values for the inter- and intra-reader agreement were 0.69 and 0.80, respectively. For tumors ≤T2, all metastatic lymph nodes were smaller than 3 mm on histopathology. Conclusion MRI after a rectal micro-enema and concurrent use of a modified staging system achieved good diagnostic performance to identify tumors suitable for LE. The rate of overstaging of local tumors was comparable to results reported in previous endorectal ultrasound (ERUS) studies.
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Ree, Anne Hansen; Benth, Jurate Saltyte; Hamre, Hanne Mari; Kersten, Christian; Hofsli, Eva & Guren, Marianne
[Show all 14 contributors for this article]
(2024).
First-line oxaliplatin-based chemotherapy and nivolumab for metastatic microsatellite-stable colorectal cancer—the randomised METIMMOX trial.
British Journal of Cancer.
ISSN 0007-0920.
130(12),
p. 1921–1928.
doi:
10.1038/s41416-024-02696-6.
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Background We evaluated first-line treatment of metastatic microsatellite-stable colorectal cancer with short-course oxaliplatin-based chemotherapy alternating with immune checkpoint blockade. Methods Patients were randomly assigned to chemotherapy (the FLOX regimen; control group) or alternating two cycles each of FLOX and nivolumab (experimental group). Radiographic response assessment was done every eight weeks with progression-free survival (PFS) as the primary endpoint. Cox proportional-hazards regression models estimated associations between PFS and relevant variables. A post hoc analysis explored C-reactive protein as signal of responsiveness to immune checkpoint blockade. Results Eighty patients were randomised and 38 in each group received treatment. PFS was comparable—control group: median 9.2 months (95% confidence interval (CI), 6.3–12.7); experimental group: median 9.2 months (95% CI, 4.5–15.0). The adjusted Cox model revealed that experimental-group subjects aged ≥60 had significantly lowered progression risk (p = 0.021) with hazard ratio 0.17 (95% CI, 0.04–0.76). Experimental-group patients with C-reactive protein <5.0 mg/L when starting nivolumab (n = 17) reached median PFS 15.8 months (95% CI, 7.8–23.7). One-sixth of experimental-group cases (all KRAS/BRAF-mutant) achieved complete response. Conclusions The investigational regimen did not improve the primary outcome for the intention-to-treat population but might benefit small subgroups of patients with previously untreated, metastatic microsatellite-stable colorectal cancer. Trial registration ClinicalTrials.gov number, NCT03388190 (02/01/2018).
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Knuth, Franziska; Tohidinezhad, Fariba; Winter, Rene Mario; Bakke, Kine Mari; Negård, Anne & Holmedal, Stein Harald
[Show all 10 contributors for this article]
(2024).
Quantitative MRI-based radiomics analysis identifies blood flow feature associated to overall survival for rectal cancer patients.
Scientific Reports.
14(1).
doi:
10.1038/s41598-023-50966-9.
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Radiomics objectively quantifies image information through numerical metrics known as features. In this study, we investigated the stability of magnetic resonance imaging (MRI)-based radiomics features in rectal cancer using both anatomical MRI and quantitative MRI (qMRI), when different methods to define the tumor volume were used. Second, we evaluated the prognostic value of stable features associated to 5-year progression-free survival (PFS) and overall survival (OS). On a 1.5 T MRI scanner, 81 patients underwent diagnostic MRI, an extended diffusion-weighted sequence with calculation of the apparent diffusion coefficient (ADC) and a multiecho dynamic contrast sequence generating both dynamic contrast-enhanced and dynamic susceptibility contrast (DSC) MR, allowing quantification of Ktrans, blood flow (BF) and area under the DSC curve (AUC). Radiomic features were extracted from T2w images and from ADC, Ktrans, BF and AUC maps. Tumor volumes were defined with three methods; machine learning, deep learning and manual delineations. The interclass correlation coefficient (ICC) assessed the stability of features. Internal validation was performed on 1000 bootstrap resamples in terms of discrimination, calibration and decisional benefit. For each combination of image and volume definition, 94 features were extracted. Features from qMRI contained higher prognostic potential than features from anatomical MRI. When stable features (> 90% ICC) were compared with clinical parameters, qMRI features demonstrated the best prognostic potential. A feature extracted from the DSC MRI parameter BF was associated with both PFS (p = 0.004) and OS (p = 0.004). In summary, stable qMRI-based radiomics features was identified, in particular, a feature based on BF from DSC MRI was associated with both PFS and OS.
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Viktil, Ellen; Hanekamp, Bettina; Nesbakken, Arild; Løberg, Else Marit; Sjo, Ole Helmer & Negård, Anne
[Show all 8 contributors for this article]
(2024).
MRI of early rectal cancer; bisacodyl micro-enema increases submucosal width, reader confidence, and tumor conspicuity.
Abdominal Radiology.
ISSN 2366-004X.
00(0),
p. 1–13.
doi:
10.1007/s00261-024-04701-1.
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Purpose To investigate the influence of a micro-enema on diagnostic performance, submucosal width, reader confidence, and tumor conspicuity using MRI to stage early rectal cancers (ERC). Methods In this single-center study, we consecutively included 50 participants with assumed ERC who all completed MRI with (MRin) and without (MRex) a micro-enema. The diagnostic performance was recorded for two experienced radiologists using histopathology as the gold standard. In addition, the width of the submucosa in the tumor-bearing wall, reader confidence for T-staging, and tumor conspicuity were assessed. Significance levels were calculated using McNemar’s test (diagnostic performance) and Wilcoxon’s signed-rank test (reader confidence, submucosal width, and conspicuity). Interreader agreement was assessed using kappa statistics. Results Sensitivity/specificity were for Reader1 91%/87% for both MRex and MRin and for Reader2 74%/87% and 89%/87%, both readers p > 0.05. The micro-enema induced a significant widening of the submucosa, p < 0.001, with a mean increase of 2.2/2.8 mm measured by Reader1/Reader2. Reader confidence in T-staging and tumor conspicuity increased for both readers, p < 0.005. The proportion of tumors with both correct staging and high reader confidence increased from 58% (29/50) to 80% (40/50) (p = 0.04) for Reader1 and from 42% (21/50) to 72% (36/50) (p = 0.002) for Reader2. Interreader agreement increased from moderate (kappa 0.58) to good (kappa 0.68). Conclusion The micro-enema significantly increased the submucosal width in the tumor-bearing wall, reader confidence, and tumor conspicuity and improved interreader agreement from moderate to good. Sensitivity and specificity in T-staging did not improve, but there was a significant increase in the proportion of tumors staged with both high confidence and correct T-stage.
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Ree, Anne Hansen; Høye, Eirik; Esbensen, Qin Ying; Beitnes, Ann-Christin Røberg; Negård, Anne & Bernklev, Linn
[Show all 16 contributors for this article]
(2024).
Complete response of metastatic microsatellite-stable BRAF V600E colorectal cancer to first-line oxaliplatin-based chemotherapy and immune checkpoint blockade.
Oncoimmunology.
ISSN 2162-4011.
13(1).
doi:
10.1080/2162402X.2024.2372886.
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The randomized METIMMOX trial (NCT03388190) examined if patients with previously untreated, unresectable abdominal metastases from microsatellite-stable (MSS) colorectal cancer (CRC) might benefit from potentially immunogenic, short-course oxaliplatin-based chemotherapy alternating with immune checkpoint blockade (ICB). Three of 38 patients assigned to this experimental treatment had metastases from BRAF-mutant MSS-CRC, in general a poor-prognostic subgroup explored here. The ≥70-year-old females presented with ascending colon adenocarcinomas with intermediate tumor mutational burden (6.2–11.8 mutations per megabase). All experienced early disappearance of the primary tumor followed by complete response of all overt metastatic disease, resulting in progression-free survival as long as 20–35 months. However, they encountered recurrence at previously unaffected sites and ultimately sanctuary organs, or as intrahepatic tumor evolution reflected in the terminal loss of initially induced T-cell clonality in liver metastases. Yet, the remarkable first-line responses to short-course oxaliplatin-based chemotherapy alternating with ICB may offer a novel therapeutic option to a particularly hard-to-treat MSS-CRC subgroup.
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Banitalebi, Hasan; Hermansen, Erland; Hellum, Christian; Espeland, Ansgar; Storheim, Kjersti & Myklebust, Tor Åge
[Show all 12 contributors for this article]
(2024).
Preoperative fatty infiltration of paraspinal muscles assessed by MRI is associated with less improvement of leg pain 2 years after surgery for lumbar spinal stenosis.
European spine journal.
ISSN 0940-6719.
33(5),
p. 1967–1978.
doi:
10.1007/s00586-024-08210-z.
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Purpose
Fatty infiltration (FI) of the paraspinal muscles may associate with pain and surgical complications in patients with lumbar spinal stenosis (LSS). We evaluated the prognostic influence of MRI-assessed paraspinal muscles’ FI on pain or disability 2 years after surgery for LSS.
Methods
A muscle fat index (MFI) was calculated (by dividing signal intensity of psoas to multifidus and erector spinae) on preoperative axial T2-weighted MRI of patients with LSS. Pain and disability 2 years after surgery were assessed using the Oswestry disability index, the Zurich claudication questionnaire and numeric rating scales for leg and back pain. Multivariate linear and logistic regression analyses (adjusted for preoperative outcome scores, age, body mass index, sex, smoking status, grade of spinal stenosis, disc degeneration and facet joint osteoarthritis) were used to assess the associations between MFI and patient-reported clinical outcomes. In the logistic regression models, odds ratios (OR) and 95% confidence intervals (CI) were calculated for associations between the MFI and ≥ 30% improvement of the outcomes (dichotomised into yes/no).
Results
A total of 243 patients were evaluated (mean age 66.6 ± 8.5 years), 49% females (119). Preoperative MFI and postoperative leg pain were significantly associated, both with leg pain as continuous (coefficient − 3.20, 95% CI − 5.61, − 0.80) and dichotomised (OR 1.51, 95% CI 1.17, 1.95) scores. Associations between the MFI and the other outcome measures were not statistically significant.
Conclusion
Preoperative FI of the paraspinal muscles on MRI showed statistically significant association with postoperative NRS leg pain but not with ODI or ZCQ.
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Bakke, Kine Mari; Meltzer, Sebastian; Grøvik, Endre; Negård, Anne; Holmedal, Stein Harald & Mikalsen, Lars Tore Gyland
[Show all 13 contributors for this article]
(2023).
Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome.
Physics and imaging in radiation oncology (PIRO).
25,
p. 1–7.
doi:
10.1016/j.phro.2023.100417.
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Background and purpose
Measuring rectal tumour response to radiation is pivotal to restaging patients and for possibly stratification to a watch-and-wait strategy. Recognizing the importance of the tumour microenvironment, we investigated a less explored quantitative imaging marker assessing tumour blood flow (BF) for its potential to predict overall survival (OS).
Materials and methods
24 rectal cancer patients given curative-intent neoadjuvant radiotherapy underwent a multi-echo dynamic magnetic resonance imaging (MRI) sequence with gadolinium contrast for quantification of tumour BF before either 25x2 Gy (n = 18) with concomitant chemotherapy or 5x5 Gy (n = 6). CD34 staining of excised tumour tissue was performed and baseline blood samples were analysed for lactate dehydrogenase (LDH) and angiopoietin-2 (ANGPT-2). Tumour volumes were measured before and after treatment. After subsequent surgery, ypTN scoring assessed tumour response. Cox regression for 5-year OS analysis and t-test for group comparisons were performed.
Results
The change in tumour BF (ΔBF) during neoadjuvant radiotherapy was a significant marker of OS, whereas tumour stage and volume were not related to OS. All patients with >20 % decline in BF were long-term survivors. Separating cases in two groups based on ΔBF revealed that patients with increase or a low decrease had higher baseline LDH (p = 0.032) and ANGPT-2 (p = 0.028) levels.
Conclusion
MRI-assessed tumour ΔBF during neoadjuvant treatment is a significant predictor of OS in rectal cancer patients, making ΔBF a potential quantitative imaging biomarker for treatment stratification. Blood LDH and ANGPT-2 indicate that non-responding tumours may have a hypoxic microenvironment resistant to radiotherapy.
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Knuth, Franziska Hanna; Grøndahl, Aurora Rosvoll; Winter, René; Torheim, Turid Katrine Gjerstad; Negård, Anne & Holmedal, Stein Harald
[Show all 10 contributors for this article]
(2022).
Semi-automatic tumor segmentation of rectal cancer based on functional magnetic resonance imaging.
Physics and imaging in radiation oncology (PIRO).
22,
p. 77–84.
doi:
10.1016/j.phro.2022.05.001.
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Background and purpose Tumor delineation is required both for radiotherapy planning and quantitative imaging biomarker purposes. It is a manual, time- and labor-intensive process prone to inter- and intraobserver variations. Semi or fully automatic segmentation could provide better efficiency and consistency. This study aimed to investigate the influence of including and combining functional with anatomical magnetic resonance imaging (MRI) sequences on the quality of automatic segmentations. Materials and methods T2-weighted (T2w), diffusion weighted, multi-echo T2*-weighted, and contrast enhanced dynamic multi-echo (DME) MR images of eighty-one patients with rectal cancer were used in the analysis. Four classical machine learning algorithms; adaptive boosting (ADA), linear and quadratic discriminant analysis and support vector machines, were trained for automatic segmentation of tumor and normal tissue using different combinations of the MR images as input, followed by semi-automatic morphological post-processing. Manual delineations from two experts served as ground truth. The Sørensen-Dice similarity coefficient (DICE) and mean symmetric surface distance (MSD) were used as performance metric in leave-one-out cross validation. Results Using T2w images alone, ADA outperformed the other algorithms, yielding a median per patient DICE of 0.67 and MSD of 3.6 mm. The performance improved when functional images were added and was highest for models based on either T2w and DME images (DICE: 0.72, MSD: 2.7 mm) or all four MRI sequences (DICE: 0.72, MSD: 2.5 mm). Conclusion Machine learning models using functional MRI, in particular DME, have the potential to improve automatic segmentation of rectal cancer relative to models using T2w MRI alone.
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Singh, Yashbir; Jons, William A.; Eaton, John E.; Vesterhus, Mette Nåmdal; Karlsen, Tom Hemming & Bjørk, Ida Torunn
[Show all 21 contributors for this article]
(2022).
Algebraic topology-based machine learning using MRI predicts outcomes in primary sclerosing cholangitis.
European Radiology Experimental.
6.
doi:
10.1186/s41747-022-00312-x.
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Background: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that can lead to cirrhosis and hepatic decompensation. However, predicting future outcomes in patients with PSC is challenging. Our aim was to extract magnetic resonance imaging (MRI) features that predict the development of hepatic decompensation by applying algebraic topology-based machine learning (ML). Methods: We conducted a retrospective multicenter study among adults with large duct PSC who underwent MRI. A topological data analysis-inspired nonlinear framework was used to predict the risk of hepatic decompensation, which was motivated by algebraic topology theory-based ML. The topological representations (persistence images) were employed as input for classification to predict who developed early hepatic decompensation within one year after their baseline MRI. Results: We reviewed 590 patients; 298 were excluded due to poor image quality or inadequate liver coverage, leaving 292 potentially eligible subjects, of which 169 subjects were included in the study. We trained our model using contrast-enhanced delayed phase T1-weighted images on a single center derivation cohort consisting of 54 patients (hepatic decompensation, n = 21; no hepatic decompensation, n = 33) and a multicenter independent validation cohort of 115 individuals (hepatic decompensation, n = 31; no hepatic decompensation, n = 84). When our model was applied in the independent validation cohort, it remained predictive of early hepatic decompensation (area under the receiver operating characteristic curve = 0.84). Conclusions: Algebraic topology-based ML is a methodological approach that can predict outcomes in patients with PSC and has the potential for application in other chronic liver diseases.
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Meltzer, Sebastian; Negård, Anne; Bakke, Kine Mari; Hamre, Hanne Mari; Kersten, Christian & Hofsli, Eva
[Show all 10 contributors for this article]
(2022).
Early radiologic signal of responsiveness to immune checkpoint blockade in microsatellite-stable/mismatch repair-proficient metastatic colorectal cancer.
British Journal of Cancer.
ISSN 0007-0920.
127,
p. 2227–2233.
doi:
10.1038/s41416-022-02004-0.
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Background: Immune checkpoint blockade (ICB) results in radiologic tumour response dynamics that differ from chemotherapy efficacy measures and require an early signal of clinical utility. Methods: Previously untreated, unresectable microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) colorectal cancer (CRC) patients were randomly assigned to the oxaliplatin-based Nordic FLOX regimen (control arm) or repeat sequential two FLOX cycles and two ICB cycles (experimental arm). The radiologic response was assessed every 8 weeks. In this post hoc analysis, we explored early target lesion (TL) dynamics as indicator of ICB responsiveness. Progression-free survival (PFS) was the primary endpoint. Results: Using a landmark analysis approach, we categorised experimental-arm patients into ≥10% (N = 19) or <10% (N = 16) TL reduction at the first post-baseline response assessment. Median PFS for the groups was 16.0 (95% confidence interval (CI), 12.3–19.7) and 3.9 months (95% CI, 2.3–5.5), respectively, superior and inferior (both P < 0.01) to the median PFS of 9.8 months (95% CI, 4.9–14.7) for control arm patients (N = 31). Conclusions: Radiologic TL reduction of ≥10% at the first post-baseline response assessment identified patients with ICB-responsive metastatic MSS/pMMR-CRC. This pragmatic measure may be used to monitor patients in investigational ICB schedules, enabling early treatment adaptation for unresponsive cases.
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Banitalebi, Hasan; Aaen, Jørn Ståle; Storheim, Kjersti; Negård, Anne; Myklebust, Tor Åge & Grotle, Margreth
[Show all 14 contributors for this article]
(2022).
A novel MRI index for paraspinal muscle fatty infiltration: reliability and relation to pain and disability in lumbar spinal stenosis: results from a multicentre study.
European Radiology Experimental.
6(1),
p. 1–10.
doi:
10.1186/s41747-022-00284-y.
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Background
Fatty infiltration of the paraspinal muscles may play a role in pain and disability in lumbar spinal stenosis. We assessed the reliability and association with clinical symptoms of a method for assessing fatty infiltration, a simplified muscle fat index (MFI).
Methods
Preoperative axial T2-weighted magnetic resonance imaging (MRI) scans of 243 patients aged 66.6 ± 8.5 years (mean ± standard deviation), 119 females (49%), with symptomatic lumbar spinal stenosis were assessed. Fatty infiltration was assessed using both the MFI and the Goutallier classification system (GCS). The MFI was calculated as the signal intensity of the psoas muscle divided by that of the multifidus and erector spinae. Observer reliability was assessed in 102 consecutive patients for three independent investigators by intraclass correlation coefficient (ICC) and 95% limits of agreement (LoA) for continuous variables and Gwet’s agreement coefficient (AC1) for categorical variables. Associations with patient-reported pain and disability were assessed using univariate and multivariate regression analyses.
Results
Interobserver reliability was good for the MFI (ICC 0.79) and fair for the GCS (AC1 0.33). Intraobserver reliability was good or excellent for the MFI (ICC range 0.86–0.91) and moderate to almost perfect for the GCS (AC1 range 0.55–0.92). Mean interobserver differences of MFI measurements ranged from -0.09 to -0.04 (LoA -0.32 to 0.18). Adjusted for potential confounders, none of the disability or pain parameters was significantly associated with MFI or GCS.
Conclusion
The proposed MFI demonstrated high observer reliability but was not associated with preoperative pain or disability.
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Borgbjerg, Jens; Larsen, Nils Eldbrønd; Salte, Ivar Mjåland; Grønli, Niklas Revold; Klæstrup, Elise & Negård, Anne
(2022).
Radiation dose in CT-based active surveillance of small renal masses may be reduced by 75%: A retrospective exploratory multiobserver study.
Research in Diagnostic and Interventional Imaging (ReDII).
doi:
10.1016/j.redii.2022.100019.
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Banitalebi, Hasan; Espeland, Ansgar; Anvar, Masoud D; Hermansen, Erland; Hellum, Christian & Brox, Jens Ivar
[Show all 14 contributors for this article]
(2022).
Reliability of preoperative MRI findings in patients with lumbar spinal stenosis.
BMC Musculoskeletal Disorders.
23(1),
p. 1–9.
doi:
10.1186/s12891-021-04949-4.
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Background
Magnetic Resonance Imaging (MRI) is an important tool in preoperative evaluation of patients with lumbar spinal stenosis (LSS). Reported reliability of various MRI findings in LSS varies from fair to excellent. There are inconsistencies in the evaluated parameters and the methodology of the studies. The purpose of this study was to evaluate the reliability of the preoperative MRI findings in patients with LSS between musculoskeletal radiologists and orthopaedic spine surgeons, using established evaluation methods and imaging data from a prospective trial.
Methods
Consecutive lumbar MRI examinations of candidates for surgical treatment of LSS from the Norwegian Spinal Stenosis and Degenerative Spondylolisthesis (NORDSTEN) study were independently evaluated by two musculoskeletal radiologists and two orthopaedic spine surgeons. The observers had a range of experience between six and 13 years and rated five categorical parameters (foraminal and central canal stenosis, facet joint osteoarthritis, redundant nerve roots and intraspinal synovial cysts) and one continuous parameter (dural sac cross-sectional area). All parameters were re-rated after 6 weeks by all the observers. Inter- and intraobserver agreement was assessed by Gwet’s agreement coefficient (AC1) for categorical parameters and Intraclass Correlation Coefficient (ICC) for the dural sac cross-sectional area.
Results
MRI examinations of 102 patients (mean age 66 ± 8 years, 53 men) were evaluated. The overall interobserver agreement was substantial or almost perfect for all categorical parameters (AC1 range 0.67 to 0.98), except for facet joint osteoarthritis, where the agreement was moderate (AC1 0.39). For the dural sac cross-sectional area, the overall interobserver agreement was good or excellent (ICC range 0.86 to 0.96). The intraobserver agreement was substantial or almost perfect/ excellent for all parameters (AC1 range 0.63 to 1.0 and ICC range 0.93 to 1.0).
Conclusions
There is high inter- and intraobserver agreement between radiologists and spine surgeons for preoperative MRI findings of LSS. However, the interobserver agreement is not optimal for evaluation of facet joint osteoarthritis.
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Meltzer, Sebastian; Kristensen, Annette Torgunrud; Abrahamsson, Hanna Josefine; Solbakken, Arne Mide; Flatmark, Kjersti & Dueland, Svein
[Show all 15 contributors for this article]
(2021).
The circulating soluble form of the CD40 costimulatory immune checkpoint receptor and liver metastasis risk in rectal cancer.
British Journal of Cancer.
ISSN 0007-0920.
125,
p. 240–246.
doi:
10.1038/s41416-021-01377-y.
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Background In colorectal cancer, the inflamed tumour microenvironment with its angiogenic activities is immune- tolerant and incites progression to liver metastasis. We hypothesised that angiogenic and inflammatory factors in serum samples from patients with non-metastatic rectal cancer could inform on liver metastasis risk. Methods We measured 84 angiogenic and inflammatory markers in serum sampled at the time of diagnosis within the population-based cohort of 122 stage I–III patients. In a stepwise manner, the statistically strongest proteins associated with time to development of liver metastasis were analysed in the corresponding serum samples from 273 stage II–III rectal cancer patients in three independent cohorts. Results We identified the soluble form of the costimulatory immune checkpoint receptor cluster of differentiation molecule 40 (sCD40) as a marker of liver metastasis risk across all patient cohorts—the higher the sCD40 level, the shorter time to liver metastasis. In patients receiving neoadjuvant treatment, the sCD40 value remained an independent variable associated with progression to liver metastasis along with the local treatment response. Of note, serum sCD40 was not associated with progression to lung metastasis. Conclusions Circulating sCD40 is a marker of liver metastasis risk in rectal cancer and may be developed for use in clinical practice.
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Knuth, Franziska Hanna; Adde, Ingvild Askim; Huynh, Bao Ngoc; Grøndahl, Aurora Rosvoll; Winter, René & Negård, Anne
[Show all 15 contributors for this article]
(2021).
MRI-based automatic segmentation of rectal cancer using 2D U-Net on two independent cohorts.
Acta Oncologica.
ISSN 0284-186X.
61(2),
p. 255–263.
doi:
10.1080/0284186X.2021.2013530.
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Background Tumor delineation is time- and labor-intensive and prone to inter- and intraobserver variations. Magnetic resonance imaging (MRI) provides good soft tissue contrast, and functional MRI captures tissue properties that may be valuable for tumor delineation. We explored MRI-based automatic segmentation of rectal cancer using a deep learning (DL) approach. We first investigated potential improvements when including both anatomical T2-weighted (T2w) MRI and diffusion-weighted MR images (DWI). Secondly, we investigated generalizability by including a second, independent cohort. Material and methods Two cohorts of rectal cancer patients (C1 and C2) from different hospitals with 109 and 83 patients, respectively, were subject to 1.5 T MRI at baseline. T2w images were acquired for both cohorts and DWI (b-value of 500 s/mm2) for patients in C1. Tumors were manually delineated by three radiologists (two in C1, one in C2). A 2D U-Net was trained on T2w and T2w + DWI. Optimal parameters for image pre-processing and training were identified on C1 using five-fold cross-validation and patient Dice similarity coefficient (DSCp) as performance measure. The optimized models were evaluated on a C1 hold-out test set and the generalizability was investigated using C2. Results For cohort C1, the T2w model resulted in a median DSCp of 0.77 on the test set. Inclusion of DWI did not further improve the performance (DSCp 0.76). The T2w-based model trained on C1 and applied to C2 achieved a DSCp of 0.59. Conclusion T2w MR-based DL models demonstrated high performance for automatic tumor segmentation, at the same level as published data on interobserver variation. DWI did not improve results further. Using DL models on unseen cohorts requires caution, and one cannot expect the same performance.
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Bakke, Kine Mari; Meltzer, Sebastian; Grøvik, Endre; Negård, Anne; Holmedal, Stein Harald & Gjesdal, Kjell-Inge
[Show all 9 contributors for this article]
(2020).
Sex differences and tumor blood flow from dynamic susceptibility contrast MRI are associated with treatment response after chemoradiation and long-term survival in rectal cancer.
Radiology.
ISSN 0033-8419.
297(2),
p. 352–360.
doi:
10.1148/RADIOL.2020200287.
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Sex differences, tumor vascularity, and blood flow seen on multiecho dynamic contrast–based MRI scans enabled prediction of treatment response and overall survival in patients with rectal cancer.
Background:
MRI is the standard tool for rectal cancer staging. However, more precise diagnostic tests that can assess biologic tumor features decisive for treatment outcome are necessary. Tumor perfusion and hypoxia are two important features; however, no reference methods that measure these exist in clinical use.
Purpose:
To assess the potential predictive and prognostic value of MRI-assessed rectal cancer perfusion, as a surrogate measure of hypoxia, for local treatment response and survival.
Materials and Methods:
In this prospective observational cohort study, 94 study participants were enrolled from October 2013 to December 2017 (ClinicalTrials.gov: NCT01816607). Participants had histologically confirmed rectal cancer and underwent routine diagnostic MRI, an extended diffusion-weighted sequence, and a multiecho dynamic contrast agent–based sequence. Predictive and prognostic values of dynamic contrast-enhanced, dynamic susceptibility contrast (DSC), and intravoxel incoherent motion MRI were investigated with response to neoadjuvant treatment, progression-free survival, and overall survival as end points. Secondary objectives investigated potential sex differences in MRI parameters and relationship with lymph node stage. Statistical methods used were Cox regression, Student t test, and Mann-Whitney U test.Results:
A total of 94 study participants (mean age, 64 years ± 11 [standard deviation]; 61 men) were evaluated. Baseline tumor blood flow from DSC MRI was lower in patients who had poor local tumor response to neoadjuvant treatment (96 mL/min/100 g ± 33 for ypT2–4, 120 mL/min/100 g ± 21 for ypT0–1; P = .01), shorter progression-free survival (hazard ratio = 0.97; 95% confidence interval: 0.96, 0.98; P < .001), and shorter overall survival (hazard ratio = 0.98; 95% confidence interval: 0.98, 0.99; P < .001). Women had higher blood flow (125 mL/min/100 g ± 27) than men (74 mL/min/100 g ± 26, P < .001) at stage 4. Volume transfer constant and plasma volume from dynamic contrast-enhanced MRI as well as ΔR2* peak and area under the curve for 30 and 60 seconds from DSC MRI were associated with local malignant lymph nodes (pN status). Median area under the curve for 30 seconds was 0.09 arbitrary units (au) ± 0.03 for pN1–2 and 0.19 au ± 0.12 for pN0 (P = .001).
Conclusion:Low tumor blood flow from dynamic susceptibility contrast MRI was associated with poor treatment response in study participants with rectal cancer.
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Ree, Anne Hansen; Nygaard, Vigdis; Pedersen, Kjetil Boye; Heinrich, Daniel; Dueland, Svein & Bergheim, Inger Riise
[Show all 25 contributors for this article]
(2020).
Molecularly matched therapy in the context of sensitivity, resistance, and safety; patient outcomes in end-stage cancer?the MetAction study.
Acta Oncologica.
ISSN 0284-186X.
p. 1–10.
doi:
10.1080/0284186X.2020.1742377.
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<i>Background</i>: In precision cancer medicine, the challenge is to prioritize DNA driver events, account for resistance markers, and procure sufficient information for treatment that maintains patient safety. The MetAction project, exploring how tumor molecular vulnerabilities predict therapy response, first established the required workflow for DNA sequencing and data interpretation (2014–2015). Here, we employed it to identify molecularly matched therapy and recorded outcome in end-stage cancer (2016–2019).<p><p> <i>Material and methods</i>: Metastatic tissue from 26 patients (16 colorectal cancer cases) was sequenced by the Oncomine assay. The study tumor boards interpreted called variants with respect to sensitivity or resistance to matched therapy and recommended single-agent or combination treatment if considered tolerable. The primary endpoint was the rate of progression-free survival 1.3-fold longer than for the most recent systemic therapy. The objective response rate and overall survival were secondary endpoints.<p><p> <i>Results</i>: Both common and rare actionable alterations were identified. Thirteen patients were found eligible for therapy following review of tumor sensitivity and resistance variants and patient tolerability. The interventions were inhibitors of ALK/ROS1-, BRAF-, EGFR-, FGFR-, mTOR-, PARP-, or PD-1-mediated signaling for 2–3 cases each. Among 10 patients who received treatment until radiologic evaluation, 6 (46% of the eligible cases) met the primary endpoint. Four colorectal cancer patients (15% of the total study cohort) had objective response. The only serious adverse event was a transient colitis, which appeared in 1 of the 2 patients given PD-1 inhibitor with complete response. Apart from those two, overall survival was similar for patients who did and did not receive study treatment.<p><p> <i>Conclusions</i>: The systematic MetAction approach may point forward to a refined framework for how to interpret the complexity of sensitivity <i>versus</i> resistance and patient safety that resides in tumor sequence data, for the possibly improved outcome of precision cancer medicine in future studies.
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Meltzer, Sebastian; Bakke, Kine Mari; Rød, Karina Lund; Negård, Anne; Flatmark, Kjersti & Solbakken, Arne Mide
[Show all 19 contributors for this article]
(2019).
Sex-related differences in primary metastatic site in rectal cancer; associated with hemodynamic factors?
Clinical and Translational Radiation Oncology.
21,
p. 5–10.
doi:
10.1016/j.ctro.2019.11.006.
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Background and purpose We investigated how features relating to pelvic cavity anatomy and tumor hemodynamic factors may influence systemic failure in rectal cancer. Materials and methods Rectal cancer patients (207 women, 343 men), who had been prospectively enrolled onto six cohorts and given curative-intent therapy, were analyzed for the first metastatic event. In one of the cohorts, the diameter of the inferior mesenteric vein (IMV) was assessed on diagnostic abdominal computed tomography images (n = 113). Tumor volume (n = 193) and histologic response to neoadjuvant therapy (n = 445) were recorded from diagnostic magnetic resonance images and surgical specimens, respectively. Results More women than men developed lung metastasis (p = 0.037), while the opposite was the case for liver metastasis (p = 0.040). Wider IMV diameter correlated with larger tumor volume (r = 0.481, p < 0.001) and male sex (p < 0.001). Female sex was the only adverse prognostic factor for lung metastasis. When sex, tumor volume, and histologic response were taken into consideration, poor tumor response remained the only determinant for liver metastasis (p = 0.002). Conclusions In a diverse rectal cancer population given curative-intent treatment, women and men had different outcome with regard to the primary metastatic site. Tumor hemodynamic factors should be considered in rectal cancer risk stratification.
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Bakke, Kine Mari; Grøvik, Endre; Meltzer, Sebastian; Negård, Anne; Holmedal, Stein Harald & Mikalsen, Lars Tore G
[Show all 11 contributors for this article]
(2019).
Comparison of Intravoxel incoherent motion imaging and multiecho dynamic contrast-based MRI in rectal cancer.
Journal of Magnetic Resonance Imaging.
ISSN 1053-1807.
50(4),
p. 1114–1124.
doi:
10.1002/jmri.26740.
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Background
Dynamic contrast‐based MRI and intravoxel incoherent motion imaging (IVIM) MRI are both methods showing promise as diagnostic and prognostic tools in rectal cancer. Both methods aim at measuring perfusion‐related parameters, but the relationship between them is unclear.
Purpose
To investigate the relationship between perfusion‐ and permeability‐related parameters obtained by IVIM‐MRI, T1‐weighted dynamic contrast‐enhanced (DCE)‐MRI and T2*‐weighted dynamic susceptibility contrast (DSC)‐MRI.
Study Type
Prospective.
Subjects
In all, 94 patients with histologically confirmed rectal cancer.
Field Strength/Sequence
Subjects underwent pretreatment 1.5T clinical procedure MRI, and in addition a study‐specific diffusion‐weighted sequence (b = 0, 25, 50, 100, 500, 1000, 1300 s/mm2) and a multiecho dynamic contrast‐based echo‐planer imaging sequence.
Assessment
Median tumor values were obtained from IVIM (perfusion fraction [f], pseudodiffusion [D*], diffusion [D]), from the extended Tofts model applied to DCE data (Ktrans, kep, vp, ve) and from model free deconvolution of DSC (blood flow [BF] and area under curve). A subgroup of the excised tumors underwent immunohistochemistry with quantification of microvessel density and vessel size.
Statistical Test
Spearman's rank correlation test.
Results
D* was correlated with BF (rs = 0.47, P < 0.001), and f was negatively correlated with kep (rs = –0.31, P = 0.002). BF was correlated with Ktrans (rs = 0.29, P = 0.004), but this correlation varied extensively when separating tumors into groups of low (rs = 0.62, P < 0.001) and high (rs = –0.06, P = 0.68) BF. Ktrans was negatively correlated with vessel size (rs = –0.82, P = 0.004) in the subgroup of tumors with high BF.
Data Conclusion
We found an association between D* from IVIM and BF estimated from DSC‐MRI. The relationship between IVIM and DCE‐MRI was less clear. Comparing parameters from DSC‐MRI and DCE‐MRI highlights the importance of the underlying biology for the interpretation of these parameters.
Level of Evidence: 2
Technical Efficacy: Stage 1
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Ree, Anne Hansen; Nygaard, Vigdis; Russnes, Hege Elisabeth Giercksky; Heinrich, Daniel; Nygaard, Vegard & Johansen, Christin
[Show all 13 contributors for this article]
(2019).
Responsiveness to PD-1 Blockade in End-Stage Colon Cancer with Gene Locus 9p24.1 Copy-Number Gain.
Cancer immunology research.
ISSN 2326-6066.
7(5),
p. 701–706.
doi:
10.1158/2326-6066.CIR-18-0777.
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Most patients whose large bowel cancer has spread to other organs do not respond to immune therapy. We detected a rare gene mutation, termed 9p24.1 copy-number gain (CNG), in an otherwise incurable colorectal cancer that provoked an immune therapy response. We identified this gene mutation by gene-panel sequencing of DNA from a liver metastasis biopsy from a patient who had disease refractory to standard therapies. Following immune checkpoint blockade (ICB) with pembrolizumab (anti–PD-1), the patient experienced conversion of the tumor phenotype from one with epithelial features to that of an inflamed microenvironment, detected by high-resolution RNA sequencing. Circulating tumor DNA disappeared over the first weeks of therapy. As assessed by standard radiographic measurement, the patient had a partial response that was durable. This patient's response may support the use of histology-agnostic ICB in solid tumors that carry the rare 9p24.1 CNG.
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Sunde, Marie Louise; Negård, Anne; Øresland, Tom; Bakka, Njål; Geitung, Jonn Terje & Færden, Arne Engebreth
(2018).
MRI defecography of the ileal pouch-anal anastomosis?contributes little to the understanding of functional outcome.
International Journal of Colorectal Disease.
ISSN 0179-1958.
33(5),
p. 609–617.
doi:
10.1007/s00384-018-3011-0.
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Ossum, Alvilde Maria; Palm, Øyvind; Kapica, Aida; Småstuen, Milada C; BANITALEBI, HASAN & Negård, Anne
[Show all 10 contributors for this article]
(2018).
Ankylosing Spondylitis and Axial Spondyloarthritis in Patients With Long-term Inflammatory Bowel Disease: Results From 20 Years of Follow-up in the IBSEN Study.
Journal of Crohn's and Colitis.
ISSN 1873-9946.
12(1),
p. 96–104.
doi:
10.1093/ecco-jcc/jjx126.
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Background Patients with inflammatory bowel disease [IBD] often suffer from rheumatic manifestations, including inflammatory back disorders. The prevalence of these disorders late in the course of IBD is poorly investigated. The aim of this study was to estimate the prevalence of inflammatory back disorders in patients with IBD 20 years after diagnosis, and to investigate possible associations with IBD severity, HLA-B27, and the NOD2 genotype. Methods A population-based cohort [the IBSEN study] was followed prospectively for 20 years. Information covering IBD activity and rheumatic diseases was collected at the regular follow-ups. HLA-B27 and NOD2 were analysed as present or absent. Results At 20 years, 599 members of the original cohort were alive, of whom 470 [78.5%] were investigated [314 ulcerative colitis and 156 Crohn’s disease patients]. Ankylosing spondylitis was diagnosed in 21 patients [4.5%], axial spondyloarthritis was diagnosed in 36 patients [7.7%], and inflammatory back pain was diagnosed in 54 patients [11.5%]. Chronic back pain [back pain > 3 months] was present in 220 patients [46.8%]. HLA-B27 was associated with ankylosing spondylitis, axial spondyloarthritis, and inflammatory back pain, whereas no significant association was found for NOD2. A more chronic IBD course was associated with axial spondyloarthritis. Conclusions Our data revealed a high prevalence of ankylosing spondylitis, axial spondyloarthritis, and inflammatory back pain 20 years after the IBD diagnosis. HLA-B27 but not NOD-2 was a predisposing factor for the inflammatory back disorders in IBD patients. Axial spondyloarthritis was associated with a more chronic active IBD disease course.
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Grøvik, Endre; Redalen, Kathrine Røe; Storås, Tryggve; Negard, Anne; Holmedal, Stein Harald & Ree, Anne Hansen
[Show all 9 contributors for this article]
(2017).
Dynamic multi-echo DCE- and DSC-MRI in rectal cancer: Low primary tumor Ktrans and ΔR2* peak are significantly associated with lymph node metastasis.
Journal of Magnetic Resonance Imaging.
ISSN 1053-1807.
46(1),
p. 194–206.
doi:
10.1002/jmri.25566.
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Purpose: To implement a dynamic contrast-based multi-echo MRI sequence in assessment of rectal cancer and evaluate associations between histopathologic data and the acquired dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) -MRI parameters. Materials and Methods: This pilot study reports results from 17 patients with resectable rectal cancer. Dynamic contrast-based multi-echo MRI (1.5T) was acquired using a three-dimensional multi-shot EPI sequence, yielding both DCE- and DSC-data following a single injection of contrast agent. The Institutional Review Board approved the study and all patients provided written informed consent. Quantitative analysis was performed by pharmacokinetic modeling on DCE data and tracer kinetic modeling on DSC data. Mann-Whitney U-test and receiver operating characteristics curve statistics was used to evaluate associations between histopathologic data and the acquired DCE- and DSC-MRI parameters. Results: For patients with histologically confirmed nodal metastasis, the primary tumor demonstrated a significantly lower Ktrans and peak change in R 2, R 2-peakenh, than patients without nodal metastasis, showing a P-value of 0.010 and 0.005 for reader 1, and 0.043 and 0.019 for reader 2, respectively. Conclusion: This study shows the feasibility of acquiring DCE- and DSC-MRI in rectal cancer by dynamic multi-echo MRI. A significant association was found between both Ktrans and R 2-peakenh in the primary tumor and histological nodal status of the surgical specimen, which may improve stratification of patients to intensified multimodal treatment.
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Negård, Anne; Løberg, Else Marit; Næss, Pål Aksel; Eriksen, Morten & Klow, Nils-Einar
(2010).
Feasibility of MRI in experimentally induced inflammatory small bowel disease: a pilot study in a porcine model.
Digestive Diseases and Sciences.
ISSN 0163-2116.
55(1),
p. 14–20.
doi:
10.1007/s10620-008-0707-y.
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Enden, Tone Rønnaug; Storås, Tryggve; Negård, Anne; HAIG, YLVA; Sandvik, Leiv & Gjesdal, Kjell-Inge
[Show all 8 contributors for this article]
(2010).
Visualization of Deep Veins and Detection of Deep Vein Thrombosis (DVT) With Balanced Turbo Field Echo (b-TFE) and Contrast-Enhanced T1 Fast Field Echo (CE-FFE) Using a Blood Pool Agent (BPA).
Journal of Magnetic Resonance Imaging.
ISSN 1053-1807.
31(2),
p. 416–424.
doi:
10.1002/jmri.22046.
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Purpose:
To assess image quality, vessel visualization, preliminary diagnostic properties, and interobserver variability of a novel balanced turbo field echo (b-TFE) sequence and contrast-enhanced T1 fast field echo (CE-FFE) sequence with blood pool agent (BPA).
Materials and Methods:
A total of 15 healthy volunteers and six patients with ultrasound-verified proximal deep vein thrombosis (DVT) were examined from the inferior vena cava (IVC) to the proximal calf veins.
Results:
The great majority of deep veins were completely visualized on both sequences. In healthy volunteers the IVC was completely visualized in five b-TFE and 11 CE-FFE scans, and partially in seven b-TFE and four CE-FFE scans (P = 0.008). Poorest image quality was in the pelvis. Contrast-to-noise ratio (CNR) was higher on b-TFE compared to CE-FFE, with significant difference in calf images (P = 0.036). Sensitivity was 100% for proximal DVT with both methods. Specificity was 70% (CE-FFE) and 80% (b-TFE) for proximal femoral DVT; 100% in distal femoral. Interobserver reliability was kappa 1.0 (b-TFE), 0.9 (CE-FFE) for proximal, and overall poor for distal DVT.
Conclusion:
Contrast-enhancement did not add valuable information in visualizing deep veins of the lower limbs compared to b-TFE, though the IVC was slightly better visualized. Diagnostic properties and interobserver reliability of both sequences were good for proximal DVT and poor for distal DVT.
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Negård, Anne; Løberg, Else Marit; Næss, Pål Aksel; Eriksen, Morten & Klow, Nils-Einar
(2010).
Feasibility of MRI in Experimentally Induced Inflammatory Small Bowel Disease: A Pilot Study in a Porcine Model.
Digestive Diseases and Sciences.
ISSN 0163-2116.
55(1),
p. 14–20.
doi:
10.1007/s10620-008-0707-y.
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Negård, Anne; Sandvik, Leiv; Berstad, AE; Paulsen, Vemund; Lygren, Idar & Borthne, Arne Sigmund
[Show all 7 contributors for this article]
(2008).
MRI of the small bowel with oral contrast or nasojejunal intubation in Crohn's disease: randomized comparison of patient acceptance.
Scandinavian Journal of Gastroenterology.
ISSN 0036-5521.
p. 44–51.
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Stenset, Vidar; Kocot, Darius; Negard, Anne; Gulbrandsen, Pål; Wallin, Anders & Fladby, Tormod
(2006).
Associations between white matter lesions, cerebrovascular risk factors and low CSF A ( beta)42.
Neurology.
ISSN 0028-3878.
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Negård, Anne; Storås, Tryggve; Borthne, A & Kløw, Nils-Einar
(2005).
Magnetic resonance imaging of the small bowel.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
125(22),
p. 3094–3097.
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Borgbjerg, Jens; Kongsrud, Tone; Negård, Anne; Krogh, Nina Rolland; Günther, Thomas & Müller, Stig
(2024).
CT-veiledet kryoablasjon av nyretumorer.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
144(15).
doi:
10.4045/tidsskr.24.0542.
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Banitalebi, Hasan; Hermansen, Erland; Hellum, Christian; Storheim, Kjersti; Indrekvam, Kari & Espeland, Ansgar
[Show all 12 contributors for this article]
(2023).
Association between preoperative fatty infiltration of the paraspinal muscles and persistent leg pain after surgery for LSS.
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Introduction: Fatty infiltration of the paraspinal muscles may have a role in clinical outcomes after decompression surgery for lumbar spinal stenosis (LSS). The purpose of this study was to evaluate the prognostic value of preoperative fatty infiltration of the paraspinal muscles assessed by MRI in postoperative pain or disability in LSS.
Materials and Methods: Prospective imaging and clinical data from the NORwegian Degenerative spondylolisthesis and spinal STENosis- spinal stenosis trial (NORDSTEN-SST) study were used. A musculoskeletal radiologist evaluated preoperative lumbar MRI examination of 300 patients with LSS scheduled for decompression surgery. Only axial T2-weighted images covering the paraspinal and the psoas muscles bilaterally were considered. Fatty infiltration of the paraspinal muscles was assessed by a muscle fat index (MFI). For this assessment, signal intensity of the multifidus and the erector spinae at the most stenotic level of lumbar spine was divided by the signal intensity of the psoas major muscle at the same level and side of spine. Pain and disability two years after surgery were assessed using patient-reported outcome measures including the Oswestry disability index (ODI, scores 0 to 100), the Zurich claudication questionnaire (ZCQ) for symptoms severity (scores 1 to 5) and function (scores 1 to 4), and numeric rating scales (NRSs) for leg and back pain (scores 1 to 10). Multivariate linear and logistic regression analyses were used to assess the relationship between the MFI and the patient-reported clinical outcomes. In the logistic regression models, odds ratios (OR) and 95% confidence intervals (CIs) were calculated for associations between the MFI and ≥ 30% improvement of the postoperative outcomes (dichotomised into yes or no).
Results: After excluding 57 patients because axial images did not cover the muscles bilaterally, images from 243 patients were evaluated. Mean age of the patients was 66.6 (±8.5) years and 119 were females (49%). Preoperative MFI and postoperative leg pain were significantly associated, both when leg pain was analysed as a continuous parameter (coefficient: -3.2, 95% CI: -5.6 to -0.8, p = 0.009) and dichotomised score (OR 62.8, 95% CI: 4.8 to 817.8, p = 0.002). These findings suggested that increased fatty infiltration in the paraspinal muscles is associated with higher risk of persistent leg pain after decompression surgery for LSS. The associations between the MFI and the other outcome measures were not statistically significant.
Conclusion: Increased preoperative fatty infiltration in the paraspinal muscles on MRI was associated with persistent leg pain two years after decompression surgery for LSS. This preoperative MRI finding may be useful as a prognostic factor in patients with LSS undergoing decompression surgery.
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Banitalebi, Hasan; Hermansen, Erland; Hellum, Christian; Storheim, Kjersti; Espeland, Ansgar & Indrekvam, Kari
[Show all 10 contributors for this article]
(2023).
Fatty Infiltration of the Paraspinal Muscles Is Associated with Postoperative Leg Pain in Lumbar Spinal Stenosis.
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Purpose To evaluate the prognostic value of MRI-assessed preoperative fatty infiltration of the paraspinal muscles in postoperative pain or disability in lumbar spinal stenosis (LSS).
Methods Prospective imaging and clinical data from the NORwegian Degenerative spondylolisthesis and spinal STENosis- spinal stenosis trial (NORDSTEN-SST) study were used. A musculoskeletal radiologist evaluated preoperative lumbar MRI examination of 300 patients with LSS scheduled for decompression surgery. Only axial T2-weighted images covering the paraspinal and the psoas muscles bilaterally were considered. Fatty infiltration of the paraspinal muscles was assessed by a muscle fat index (MFI). For this assessment, signal intensity of the multifidus and the erector spinae at the most stenotic level of lumbar spine was divided by the signal intensity of the psoas major muscle at the same level and side of spine. Pain and disability two years after surgery were assessed using patient-reported outcome measures including the Oswestry disability index (ODI, scores 0 to 100), the Zurich claudication questionnaire (ZCQ) for symptoms severity (scores 1 to 5) and function (scores 1 to 4), and numeric rating scales (NRSs) for leg and back pain (scores 1 to 10). Multivariate linear and logistic regression analyses were used to assess the relationship between the MFI and the patient-reported clinical outcomes. In the logistic regression models, odds ratios (OR) and 95% confidence intervals (CIs) were calculated for associations between the MFI and ≥ 30% improvement of the postoperative outcomes (dichotomised into yes or no).
Results After excluding 57 patients because axial images did not cover the muscles bilaterally, images from 243 patients were evaluated. Mean age of the patients was 66.6 (±8.5) years and 119 were females (49%). Preoperative MFI and postoperative leg pain were significantly associated, both when leg pain was analysed as a continuous parameter (coefficient: -3.2, 95% CI: -5.6 to -0.8, p = 0.009) and dichotomised score (OR 62.8, 95% CI: 4.8 to 817.8, p = 0.002). These findings suggested that increased fatty infiltration in the paraspinal muscles is associated with higher risk of persistent leg pain after decompression surgery for LSS. The associations between the MFI and the other outcome measures were not statistically significant.
Conclusion Increased preoperative fatty infiltration in the paraspinal muscles on MRI was associated with persistent leg pain two years after decompression surgery for LSS. This preoperative MRI finding may be useful as a prognostic factor in patients with LSS undergoing decompression surgery.
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Meltzer, Sebastian; Negård, Anne; Hamre, Hanne Mari; Kersten, Christian; Hofsli, Eva & Guren, Marianne Grønlie
[Show all 9 contributors for this article]
(2022).
Early radiologic signal of nivolumab responsiveness after short-course oxaliplatin-based chemotherapy in microsatellite-stable (MSS) metastatic colorectal cancer (mCRC).
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Mortensen, Joachim Høg; Lunder, Aida Kapic; Manon-Jensen, Tina; Karsdal, MA; Nielsen, Mette & Leeming, DJ
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P117 Biomarkers of extracellular matrix remodelling are associated with intestinal fibrosis assessed by magnetic resonance enterography and accumulated intestinal damage (Lémann index): the IBSEN study.
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Lunder, Aida Kapic; Bakstad, Linda Tøften & Negård, Anne
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Detection of Bowel lesions in newly diagnosed patients with Crohn`s disease by MR Enterography versus ileocolonoscopy.
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Frøyen, Elin Agathe; Lyckander, Lars Gustav; Grandal, Ole Jacob; Lunder, Aida Kapic; Meltzer, Sebastian & Redalen, Kathrine
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MRI of Extramural Venous Invasion in rectal cancer: assessment of the interobserver agreement and comparison with histopathology stained with hematoxylin/eosin and elastin.
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Lunder, Aida Kapic; Bakstad, Linda Tøften & Negård, Anne
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Magnetic resonance Imaging assessment of newly diagnosed patients with Crohns disease un a population-based cohort of patients in Norway (Ibsen III).
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Lunder, Aida Kapic; Jahnsen, Jørgen; T, Linda Bakstad; Borthne, Arne Sigmund; Hov, Johannes Espolin Roksund & Vatn, Morten H
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Negard, Anne; Redalen, Kathrine Røe; Jahnsen, Jørgen; Færden, Arne Engebret; Ree, Anne Hansen & Vatn, Morten H
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Crohns disease and secondary malignancy: Morphological findings with MRI and CT and how novel functional MR sequences can improve diagnostics.
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BANITALEBI, HASAN & Negård, Anne
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Institute of clinical medicine, faculty of Medicine, university of Oslo.
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Published
Sep. 5, 2017 10:10 AM
- Last modified
Aug. 7, 2018 9:58 AM
