| 1. |
- Montelius, Mikael, 1979, et al.
(författare)
-
Multiparametric MRI with spatiotemporal evaluation reveals potential therapy response biomarkers for 177Lu-octreotate therapy of mice with human neuroendocrine tumor
- 2017
-
Ingår i: ISMRM 25th Annual Meeting. 22-27 April 2017, Honolulu, Hawaii, USA.
-
Konferensbidrag (refereegranskat)abstract
- Tissue parameters derived from multiparametric MRI were evaluated as potential imaging biomarkers for therapy response assessment in mice with human neuroendocrine tumor treated with 177Lu-octreotate. Animals were imaged before and repeatedly after 177Lu-octreotate treatment, using T2w, IVIM-DWI, DCE-MRI, T1- and T2*-mapping techniques. MR-parameters were evaluated regionally and longitudinally, and quantitative proteomics was used to evaluate underlying biological response in central and peripheral tumor separately. Several MR-parameters showed strong correlation with tumor response, as verified by MRI-based tumor volume measurements, but also with proteins associated with radiobiological effects on tumor tissue. Spatial and temporal evaluation increased sensitivity of the methods.
|
|
| 2. |
- Spetz, Johan, et al.
(författare)
-
Spatial proteomic analysis of GOT1 human small intestine neuroendocrine tumor in nude mice following 177Lu-octreotate therapy
- 2016
-
Ingår i: 62nd Annual International Meeting Radiation Research Society, Waikoloa, HI, USA, October 16-19, 2016.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: 177Lu-octreotate can be used for therapy of somatostatin receptor expressing neuroendocrine tumors (NET). 177Lu-octreotate therapy has achieved high cure rates in GOT1 (human small intestine NET) transplanted to nude mice. However, clinical studies result in moderate response, and complete tumor remission is rarely seen. Solid tumors often develop necrotic cores during growth due to e.g. insufficient vascularization, which may account for the different uptake kinetics and varying therapeutic success seen after 177Lu-octreotate treatment. It is therefore important to explore the cellular effects of 177Lu-octreotate to further optimize treatment parameters and identify biomarkers for treatment response assessment. Aim: To detect significant changes in protein profiles from peripheral and central samples of GOT1 tumor after 177Lu-octreotate therapy. Methods: GOT1 bearing BALB/c nude mice were i.v. injected with 15 MBq 177Lu-octreotate (corresponding to 4 Gy tumor absorbed dose) and killed after 13 days. Total cellular proteins were extracted from the peripheral and central parts of surgically excised tumor samples. Proteomic profiling was generated using liquid chromatography tandem-mass spectrometry (LC-MS/MS), followed by database-based protein identification and relative quantification. Functional annotation of proteins was performed using the DAVID bioinformatics resource tool. Results: The LC-MS/MS analysis identified 58 differentially expressed proteins (p<0.05, Fold Change>1.2) between the peripheral and central parts of tumor samples. Forty of these showed higher levels in the peripheral compared with the central samples, and among them were proteins associated with blood vessel/vasculature development (e.g. FAK1, H6ST1, LMA4, and SYWM), regulation of cell cycle and apoptosis (e.g. FAK1 and MK01), and cellular integrity (e.g. PDLI5, CALD1, FERM2, and NEB2). Conclusions: Taken together, these findings suggest spatial differences in tumor response to 177Lu-octreotate, mainly constituted by differences in vascularization and cellular integrity. These findings indicate potential venues for prognostic evaluation of NET therapy using 177Lu-octreotate. However, further studies are needed to determine whether these effects are time- and/or dose-dependent.
|
|
| 3. |
- Andersson, M., et al.
(författare)
-
Evaluation of response in patients with hepatocellular carcinoma treated with intratumoral dendritic cell vaccination using intravoxel incoherent motion (IVIM) MRI and histogram analysis
- 2023
-
Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 64:1, s. 32-41
-
Tidskriftsartikel (refereegranskat)abstract
- Background Immunotherapy of hepatocellular carcinoma (HCC) is an emerging method with promising results. Immunotherapy can have an antitumor effect without affecting tumor size, calling for functional imaging methods for response evaluation. Purpose To evaluate the response to intratumoral injections with the immune primer ilixadencel in HCCs with diffusion-weighted magnetic resonance imaging (DW-MRI) using intravoxel incoherent motion (IVIM) and histogram analysis. Material and Methods A total of 17 patients with advanced HCC were treated with intratumoral injections with ilixadencel on three occasions 2-5 weeks apart. The patients were examined with IVIM before each injection as well as approximately three months after the first injection. Results The 10th percentile of perfusion-related parameter D* decreased significantly after the first and second intratumoral injections of ilixadencel compared to baseline (P < 0.05). There was a non-significant trend of lower median region of interest f (perfusion fraction) before injection 2 compared to baseline (P = 0.07). There were significant correlations between the 10th percentile and median of D at baseline and change in tumor size after three months (r = 0.79, P < 0.01 and r = 0.72, P < 0.05, respectively). Conclusion DW-MRI with IVIM and histogram analysis revealed significant reductions of D* early after treatment as well as an association between D at baseline and smaller tumor growth at three months. The lower percentiles (10th and 50th) were found more important. Further research is needed to confirm our preliminary findings of reduced perfusion after ilixadencel vaccinations, suggesting a treatment effect on HCC.
|
|
| 4. |
- Montelius, Mikael, 1979, et al.
(författare)
-
Identification of Potential MR-Derived Biomarkers for Tumor Tissue Response to 177Lu-Octreotate Therapy in an Animal Model of Small Intestine Neuroendocrine Tumor.
- 2018
-
Ingår i: Translational oncology. - : Elsevier BV. - 1936-5233. ; 11:2, s. 193-204
-
Tidskriftsartikel (refereegranskat)abstract
- Magnetic resonance (MR) methods enable noninvasive, regional tumor therapy response assessment, but associations between MR parameters, underlying biology, and therapeutic effects must be investigated.The aim of this study was to investigate response assessment efficacy and biological associations of MR parameters in a neuroendocrine tumor (NET) model subjected to radionuclide treatment.Twenty-one mice with NETs received 177Lu-octreotate at day 0. MR experiments (day -1, 1, 3, 8, and 13) included T2-weighted, dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) and relaxation measurements (T1/T2*). Tumor tissue was analyzed using proteomics. MR-derived parameters were evaluated for each examination day and for different radial distances from the tumor center. Response assessment efficacy and biological associations were evaluated using feature selection and protein expression correlations, respectively.Reduced tumor growth rate or shrinkage was observed until day 8, followed by reestablished growth in most tumors. The most important MR parameter for response prediction was DCE-MRI-derived pretreatment signal enhancement ratio (SER) at 40% to 60% radial distance, where it correlated significantly also with centrally sampled protein CCD89 (association: DNA damage and repair, proliferation, cell cycle arrest). The second most important was changed diffusion (D) between day -1 and day 3, at 60% to 80% radial distance, where it correlated significantly also with peripherally sampled protein CATA (association: oxidative stress, proliferation, cell cycle arrest, apoptotic cell death).Important information regarding tumor biology in response to radionuclide therapy is reflected in several MR parameters, SER and D in particular. The spatial and temporal information provided by MR methods increases the sensitivity for tumor therapy response.
|
|
| 5. |
- Jalnefjord, Oscar, 1989, et al.
(författare)
-
Data-driven identification of tumor subregions based on intravoxel incoherent motion reveals association with proliferative activity
- 2019
-
Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 82:4, s. 1480-1490
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Intravoxel incoherent motion (IVIM) analysis gives information on tissue diffusion and perfusion and may thus have a potential for e.g. tumor tissue characterization. This work aims to study if clustering based on IVIM parameter maps can identify tumor subregions, and to assess the relevance of obtained subregions by histological analysis. Methods: Fourteen mice with human neuroendocrine tumors were examined with diffusion-weighted imaging to obtain IVIM parameter maps. Gaussian mixture models with IVIM maps from all tumors as input were used to partition voxels into k clusters, where k = 2 was chosen for further analysis based on goodness of fit. Clustering was performed with and without the perfusion-related IVIM parameter D*, and with and without including spatial information. The validity of the clustering was assessed by comparison with corresponding histologically stained tumor sections. A Ki-67-based index quantifying the degree of tumor proliferation was considered appropriate for the comparison based on the obtained cluster characteristics. Results: The clustering resulted in one class with low diffusion and high perfusion and another with slightly higher diffusion and low perfusion. Strong agreement was found between tumor subregions identified by clustering and subregions identified by histological analysis, both regarding size and spatial agreement. Neither D* nor spatial information had substantial effects on the clustering results. Conclusions: The results of this study show that IVIM parameter maps can be used to identify tumor subregions using a data-driven framework based on Gaussian mixture models. In the studied tumor model, the obtained subregions showed agreement with proliferative activity.
|
|
| 6. |
- Montelius, Mikael, 1979, et al.
(författare)
-
Tumour size measurement in a mouse model using high resolution MRI.
- 2012
-
Ingår i: BMC medical imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Animal models are frequently used to assess new treatment methods in cancer research. MRI offers a non-invasive in vivo monitoring of tumour tissue and thus allows longitudinal measurements of treatment effects, without the need for large cohorts of animals. Tumour size is an important biomarker of the disease development, but to our knowledge, MRI based size measurements have not yet been verified for small tumours (102-101g). The aim of this study was to assess the accuracy of MRI based tumour size measurements in small tumours on mice. METHODS: 2D and 3D T2-weighted RARE images of tumour bearing mice were acquired in vivo using a 7 T dedicated animal MR system. For the 3D images the acquired image resolution was varied. The images were exported to a PC workstation where the tumour mass was determined assuming a density of 1 g/cm3, using an in-house developed tool for segmentation and delineation. The resulting data were compared to the weight of the resected tumours after sacrifice of the animal using regression analysis. RESULTS: Strong correlations were demonstrated between MRI-and necropsy determined masses. In general, 3D acquisition was not a prerequisite for high accuracy. However, it was slightly more accurate than 2D when small (<0.2 g) tumours were assessed for inter-and intraobserver variation. In 3D images, the voxel sizes could be increased from 1603um3 to 2403um3 without affecting the results significantly, thus reducing acquisition time substantially. CONCLUSIONS: 2D MRI was sufficient for accurate tumour size measurement, except for small tumours (<0.2g) where 3D acquisition was necessary to reduce interobserver variation. Acquisition times between 15 and 50 minutes, depending on tumour size, were sufficient for accurate tumour volume measurement. Hence, it is possible to include further MR investigations of the tumour, such as tissue perfusion, diffusion or metabolic composition in the same MR session.
|
|
| 7. |
|
|
| 8. |
- Starck, Göran, et al.
(författare)
-
A 1H magnetic resonance spectroscopy study in adults with obsessive compulsive disorder: relationship between metabolite concentrations and symptom severity.
- 2008
-
Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 115:7, s. 1051-62
-
Tidskriftsartikel (refereegranskat)abstract
- 1H magnetic resonance spectroscopy (1H MRS) studies exploring brain metabolites, especially glutamine + glutamate (Glx), in obsessive compulsive disorder (OCD) are of vital interest for trying to understand more about the pathophysiology of OCD. Therefore, we conducted the present 1H MRS study with the aims of (1) comparing MRS metabolites in a group of adult patients with OCD and a group of healthy controls, and (2) examining the relationship between MRS metabolite concentrations and symptom severity in the patient group. Three brain regions were studied, the right caudate nucleus, the anterior gyrus cinguli and the occipital cortex bilaterally. Since multivariate analysis is a highly useful tool for extraction of 1H MRS data, we applied principal component analysis (PCA) and partial least square projection to latent structures (PLS) to the MRS data. PLS disclosed a strong relationship between several of the metabolites and OCD symptom severity, as measured with Yale-Brown obsessive-compulsive scale (YBOCS): the YBOCS score was found to be positively correlated to caudate creatine, Glx, glutamate, and choline compounds as well as occipital cortex myoinositol, and negatively correlated to occipital cortex Glx. The negative correlation between occipital cortex Glx and YBOCS was the most impressive. PCA did not reveal any tendency for a separation between the patients with OCD and controls with respect to MRS metabolites. The results are discussed in relation to corticostriatothalamocortical feedback and previous observations of poor visuospatial ability in OCD.
|
|
| 9. |
- Lilja, Ylva, et al.
(författare)
-
Visual pathway impairment by pituitary adenomas: quantitative diagnostics by diffusion tensor imaging.
- 2017
-
Ingår i: Journal of neurosurgery. - 1933-0693. ; 127:3, s. 569-579
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Despite ample experience in surgical treatment of pituitary adenomas, little is known about objective indices that may reveal risk of visual impairment caused by tumor growth that leads to compression of the anterior visual pathways. This study aimed to explore diffusion tensor imaging (DTI) as a means for objective assessment of injury to the anterior visual pathways caused by pituitary adenomas. METHODS Twenty-three patients with pituitary adenomas, scheduled for transsphenoidal tumor resection, and 20 healthy control subjects were included in the study. A minimum suprasellar tumor extension of Grade 2-4, according to the SIPAP (suprasellar, infrasellar, parasellar, anterior, and posterior) scale, was required for inclusion. Neuroophthalmological examinations, conventional MRI, and DTI were completed in all subjects and were repeated 6 months after surgery. Quantitative assessment of chiasmal lift, visual field defect (VFD), and DTI parameters from the optic tracts was performed. Linear correlations, group comparisons, and prediction models were done in controls and patients. RESULTS Both the degree of VFD and chiasmal lift were significantly correlated with the radial diffusivity (r = 0.55, p < 0.05 and r = 0.48, p < 0.05, respectively) and the fractional anisotropy (r = -0.58, p < 0.05 and r = -0.47, p < 0.05, respectively) but not with the axial diffusivity. The axial diffusivity differed significantly between controls and patients with VFD, both before and after surgery (p < 0.05); however, no difference was found between patients with and without VFD. Based on the axial diffusivity and fractional anisotropy, a prediction model classified all patients with VFD correctly (sensitivity 1.0), 9 of 12 patients without VFD correctly (sensitivity 0.75), and 17 of 20 controls as controls (specificity 0.85). CONCLUSIONS DTI could detect pathology and degree of injury in the anterior visual pathways that were compressed by pituitary adenomas. The correlation between radial diffusivity and visual impairment may reflect a gradual demyelination in the visual pathways caused by an increased tumor effect. The low level of axial diffusivity found in the patient group may represent early atrophy in the visual pathways, detectable on DTI but not by conventional methods. DTI may provide objective data, detect early signs of injury, and be an additional diagnostic tool for determining indication for surgery in cases of pituitary adenomas.
|
|
| 10. |
- Ljungberg, Maria, et al.
(författare)
-
31P MR spectroscopy to evaluate the efficacy of hepatic artery embolization in the treatment of neuroendocrine liver metastases.
- 2012
-
Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 53:10, s. 1118-1126
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundIt is common to treat patients with metastatic disease from gastrointestinal neuroendocrine (NE) tumors with surgical reduction to prolong survival. This can be combined with hepatic arterial embolization (HAE) and medical treatment to reduce hormonal symptoms. Today there are no rapid and reliable methods to evaluate the efficacy of HAE in the treatment of neuroendocrine liver metastasis.PurposeTo investigate metabolic changes in hepatic metastases of NE tumors following HAE, and to establish if there are any early spectral patterns that might indicate therapeutic efficacy based on in vivo (31)P MRS data.Material and MethodsVolume selective (31)P MRS was used to study 11 patients with disseminated NE tumors with regional lymph nodes and bilobar liver metastases. Measurements were performed before and 1 and 3 days after HAE.ResultsNon-responders had significantly higher PME/Pi and αNTP/ΣNTP ratios than the responders before HAE (P < 0.05). Three days after HAE, non-responders still had significantly higher αNTP/ΣNTP than the responders did (P < 0.05). We also observed trends for increased PME ratios 3 days after HAE, decreased ATP-levels, and liberated Pi in responders.ConclusionThis (31)P-MRS study showed significant differences in PME/Pi and αNTP/ΣP ratios between responders and non-responders on the day before HAE, which is an interesting finding that may reflect intrinsic properties of the tumor tissue. We also observed trends for cell membrane renewal and increased energy consumption in responders after HAE. These results demonstrate potentials for (31)P-MRS to predict individual responsiveness prior to HAE.
|
|
