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IVIM reveals increased blood perfusion of liver metastases after oral intake of Salovum®

Conference contribution
Authors Mikael Montelius
Oscar Gustafsson
Mats Andersson
Eva Forssell-Aronsson
Ragnar Hultborn
Susanne Ottosson
Göran Carlsson
Stefan Lange
Maria Ljungberg
Published in Magnetic Resonance Materials in Physics, Biology and Medicine. ESMRMB 2015, 32nd Annual Scientific Meeting, Edinburgh, UK, 1-3 October
ISSN 0968-5243
Publication year 2015
Published at Institute of Clinical Sciences, Department of Radiation Physics
Institute of Clinical Sciences, Department of Surgery
Institute of Clinical Sciences, Department of Oncology
Institute of Clinical Sciences, Department of Radiology
Institute of Biomedicine, Department of Infectious Medicine
Language en
Keywords DWI, IVIM, MRI, Salovum, Colorectal cancer, response assessment, diffusion, perfusion
Subject categories Cancer and Oncology


Introduction Elevated interstitial fluid pressure (IFP) of tumours impairs perfusion, which hinders anti-cancer drugs and oxygen to reach tumour cells1-3. AF-16, a 16 amino acid long sequence from the amino terminal end of the endogenous protein Antisecretory Factor (AF), supresses IFP in animal models of solid tumours4, and could improve drug delivery to tumour cells. Salovum®, a spray-dried egg yolk powder with high content of antisecretory peptides, should be tested on humans, but requires non-invasive tumour IFP/perfusion assessment methods. The IntraVoxel Incoherent Motion (IVIM) model applied to multi-b DWI enables measurement of tissue diffusion (D), pseudo-diffusion (D*) and voxel volume fraction of actively perfused capillaries (f) 5. The aim of this study was to investigate if f could be used to monitor changes induced by Salovum® in colorectal liver metastases in vivo Subjects and Methods Previously untreated patients (n=6) with colorectal liver metastases were imaged before, and 24h after intake of Salovum®, using IVIM-MRI (3T Philips, 16‐channel receiver; Single-shot, SE‐EPI (breath-hold); FOV covering liver, 3x3x5mm3 voxels; TR/TE/NSA/SENSE=1900ms/50ms/2/2; 11 b‐values (0-600); acquisition~10 min. MATLAB-based images processing comprised 1) Inter-scan image registration (volume preserving free-form deformation6); 2) Voxelwise fitting of D and A [eq.2] to S(b200-600) (for b>200, [eq.1] reduces to [eq.2], assuming D<2cm) on DWI (b=600), transfer of ROIs to corresponding f-maps for calculation of median ROI f before and after Salovum® intake and 4) Mann-Whitney U-test for statistical significance (α-level=0.05). Results Liver and metastases were well visualised on DWIs and f-maps Median f in metastatic tissue increased after intake of Salovum® in 5/6 patients, but decreased in one patient (Fig.2) (p<0.0001). Discussion/Conclusion The increased perfusion fraction on day 2 may offer a “window of opportunity” for improved transport of drugs to tumour cells. The increase in f was small, and perhaps not clinically significant, suggesting that additional time points after Salovum® intake and dose escalation be investigated, as well as intra-tumour effect heterogeneity. The proposed IVIM approach is a promising, non-invasive method for studying Salovum® induced changes in liver metastases in vivo. Further optimisation and fractionation studies should be conducted, and IVIM derived parameters should be compared to other techniques for perfusion or IFP measurements. References 1Rofstad,E.K.,et al.,Neoplasia. 2009;11(11):1243-51. 2Milosevic,M.F.,et al.,1999;43(5):1111-23. 3Wiig, H.,et al.,1982;42(2):159-64. 4Al-Olama, al., 2011;50(7):1098-104. 5Le Bihan, D., et al., 1988;168(2):497-505. 6Rueckert, D., et al., 1999;18(8):712-21.

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