Study (year) / Tumour model / Treatment administered / Validation method / MRI-based VSI (µm) / Validation VSI (µm) / Correlation / MRI-based NmVD±SD in µm (n) / ValidationNmVD±SD* in µm (n)
Dennie et al. (1998)S1 / Rat; C6 glioma / None / Histology / NQ / 6.25±3.4 / ND / 1.92±0.24 (4) / 1.89±1.19 (3)
Remy et al. (2000)S2 / Rat; C6 glioma / None / Histology / NQ / NQ / QA / NQ / NQ
Badruddoja et al. (2003)S3 / Rat; 9L gliosarcoma / Dexamethasone / Histology / NQ / 3.15±0.42 / ND / 1.91±1.26 (17) / 1.88±0.28 (13)
Control / Histology / NQ / 5.33±0.46 / ND / 5.37±3.56 (10) / 2.97±0.32 (7)
Packard et al. (2003)S4 / Rat; U87 glioma‡ / None / Histology / NQ / 8.4±0.65 / ND / 1.52±0.63 (14) / 1.63±0.14 (6)
Robinson et al. (2003)S5 / Mouse; RIF-1 fibrosarcoma / None / Histology / 5–11 / NQ / QA / NQ / NQ
Mouse; GH3 prolactinoma / None / Histology / 14–21 / NQ / QA / NQ / NQ
Tropres et al. (2004)S6 / Rat; C6 glioma / None / Histology / 20.0±6.3 / 5.8±4.1 / ρs=0.74 / 2.70±0.65 (7) / 1.87±1.54 (7)
Zwick et al. (2007)S7 / Mouse; HaCaT-ras-A-5RT3 human skin carcinoma / DC101 / Histology / 250 / NQ / QA / NQ / NQ
Control / Histology / 350 / NQ / QA / NQ / NQ
Valable et al. (2008)S8 / Rat; C6 glioma / None / Histology / 19.5±4.8 / 9.9±2.1 / R2=0.85, P<0.001 / 2.18±0.50 (12) / 2.68±0.61 (12);P=0.039
Rat; RG2 glioma / None / histology / 11.0±2.0 / 7.4±1.3 / R2=0.85, P<0.001 / 1.79±0.42 (12) / 1.90±0.39 (12)
Serduc et al. (2008)S9 / Mouse; 9L gliosarcoma / Radiation / Histology / NQ / NQ / QA / NQ / NQ
Robinson et al. (2008)S10 / Mouse; B16 melanoma / Control / Ex vivo FM / 13.5±1 / 32±2 / ND / NQ / NQ
PDGF upregulation / Ex vivo FM / 10.3±1 / 21±1 / ND / NQ / NQ
Beaumont et al. (2009)S11 / Rat; C6 glioma / None / Histology / 14.4±1.5 / 5.4±0.6 / ND / 2.82±0.34 (14) / 1.59±0.20 (6)
Rat; RG2 glioma / None / Histology / 8.7±0.7 / 5.8±0.4 / ND / 1.71±0.17 (6) / 1.71±0.15 (6)
Zwick et al. (2009)S12 / Mouse; HaCaT-ras-A-5RT3 human skin carcinoma / Bevacizumab / Histology / 70±15 / 19±12 / ND / NQ / NQ
Control / Histology / 57±14 / 19±13 / ND / NQ / NQ
Mouse; A431 human skin carcinoma / Sunitinib / Histology / 50±11 / 29±5 / ND / NQ / NQ
Control / Histology / 42±10 / 20±6 / ND / NQ / NQ
Yung et al. (2009)S13 / Mouse; human pancreatic adenocarcinoma / None / Histology / 11 / NQ / ρs=0.898, P=0.038 / NQ / NQ
Farrar et al. (2010)S14 / Mouse; U87 glioma / None / Histology / NQ / 6.43±0.95 / ND / 1.64±0.10 (4) / 1.67±0.67 (4)
Intravital microscopy / NQ / 11.50±0.8 / ND / 1.39±0.17 (7)§ / 1.37±0.08 (5)§
Ungersma et al. (2010)S15 / Mouse; HM7 colorectal cancer / G6-31 and anti-NRP1 / Histology / 32.6±1.7 / NQ / R2=0.45, p<0.01 / NQ / NQ
Ex vivo micro-CT / 32.6±1.7 / 30.9±0.7 / R2=0.61, p<0.01 / NQ / NQ
Douma et al. (2010)S16 / Mouse; LS174T colorectal cancerǀǀ / None / Ex vivo 3D LSM / 34.3 (22.8–47.8)¤ / 4.3 (3.1–4.8)¤ / ND / 2.88 (8§) / 1.95 (11§)
Bauerle et al. (2010)S17 / Rat; MDA-MB-231 breast cancer / Zoledronic acid / Histology / 56 / 10.89 / ND / NQ / NQ
Sunitinib malate / Histology / 75 / 18.33 / ND / NQ / NQ
Zoledronic acid + Sunitinib / Histology / 69 / 17.27 / ND / NQ / NQ
Merz et al. (2011)S18 / Rat; bone metastases from MDA-MB-231 breast cancer cells / Sorafenib tosylate / Histology / 69±4 / 15.02±8.40 / ND / NQ / NQ
Paclitaxel / Histology / 32±4 / 8.66±3.30 / ND / NQ / NQ
Sorafenib + placlitaxel / Histology / 66±7 / 15.40±6.89 / ND / NQ / NQ
Control / Histology / 43±3 / 9.86±3.36 / ND / NQ / NQ
Ullrich et al. (2011)S19 / Mouse; non-small-cell lung carcinoma / PTK787 / Histology / NQ / NQ / R2=0.8, P<0.001 (MVD) / NQ / NQ
Lemasson et al. (2011)S20 / Rat; U87 glioma / Control / Histology / 7.9±1.2 / 5.2±0.6 / ND / 1.20±0.19 (4) / 1.24±0.15 (4)
BCNU / Histology / 7.9±1.2 / 5.4±0.6 / ND / 1.20±0.19 (4) / 1.29±0.16 (4)
Sorafenib / Histology / 12.4±1.7 / 5.8±0.7 / ND / 1.55±0.23 (4) / 1.38±0.17 (4)
Yuan et al. (2011)S21 / Mouse; CL1-0/VEGF121 human lung adenocarcinoma / None / Histology / 37.24±4.88 / NQ / QA / NQ / NQ
Mouse; CL1-0/VEGF165 human lung adenocarcinoma / None / Histology / 28.84±1.46 / NQ / QA / NQ / NQ
Mouse; CL1-0/VEGF189 human lung adenocarcinoma / None / Histology / 18.82±2.27 / NQ / QA / NQ / NQ
Mouse; CL1-0/Mock human lung adenocarcinoma / None / Histology / 9.84±2.25 / NQ / QA / NQ / NQ
Just (2011)S22 / Rat; GLM, 9L, C6, U87-MG and human glioma / None / Histology / NQ / NQ / QA / NQ / NQ
Remmele et al. (2011)S23 / Mouse; HT1080 human breast fibrosarcoma / None / Phantom, Histology / 13.4±9.4 / 17.23±8.43 / ND / NQ / NQ
Wyatt et al. (2011)S24 / Mouse; HM7 colorectal carcinoma / PI3K/mTOR / Ex vivo micro-CT / NQ / NQ / QA / NQ / NQ
Nielsen et al. (2012)S25 / Mouse; C3H mammary carcinoma / CA4P / Histology / NQ / NQ / ¶ / NQ / NQ
Walker-Samuel et al. (2012)S26 / Mouse; PC3LN3 prostate carcinoma / Control / Histology / 40.3 / 49.4 / ND / NQ / NQ
ZD6126 / Histology / 34.2 / 48.1 / ND / NQ / NQ
Burrell et al. (2012)S27 / Mouse; SW1222 colorectal carcinoma / ZD6126 / Ex vivo micro-CT / 23.3±3 / 28.4±4 / ND / NQ / NQ
Control / Ex vivo micro-CT / 24.3±2 / 24.5±2 / ND / NQ / NQ
Jin et al. (2012)S28 / Rat; McA-RH7777 and N1-S1 hepatocellular carcinoma / None / Histology / NQ / NQ / R2=0.574, P<0.05 / NQ / NQ
Boult et al. (2012)S29 / Mouse; PC3 prostate carcinoma / Saracatinib / histology / 51±8 / NQ / QA / NQ / NQ
Control / histology / 52±11 / NQ / ND / NQ / NQ
Kim et al. (2013)S30 / Mouse; MDA-MB-231 breast cancer / None (week 3) / Ex vivo micro-CT / ~19# / ~10.2# / ρs=0.758, P=0.011 / NQ / NQ
None (week 5) / Ex vivo micro-CT / ~32# / ~10.4# / ND / NQ / NQ
Lemasson et al. (2013)S31 / Rat; C6 glioma / None / Histology / 10.9±4.2 / 7.9±2.1 / R2=0.73, P<0.001 / 1.62±0.46 (15) / 1.69±0.23 (15)
Rat; RG2 glioma / None / Histology / 6.6±2.7 / 6.1±1.6 / R2=0.73, P<0.001 / 1.44±0.48 (12) / 1.30±0.30 (12)
Boult et al. (2013)S32 / Mouse; C6 glioma / Tandutinib / Histology / 21.9±4.7 / 28.1±0.3 / QA / NQ / NQ
Control / Histology / 23.8±2.7 / 29.1±0.4 / QA / NQ / NQ
Viel et al. (2013)S33 / Rat; human glioblastoma spheroids / Bevacizumab / Histology / 28.5±10.7 / ND / QA / 3.42±0.68 (4) / NQ
Control / Histology / 16.6±2.1 / ND / QA / 2.13±0.33 (4) / NQ
Persigehl et al. (2013)S34 / Mouse; DU-4475 breast cancer / None / Histology / 20.6±4.9 / 9.6±2.1 / QA / NQ / NQ
Intravital microscopy / 20.6±4.9 / 9.1±6.7 / QA / NQ / NQ
Mouse; MDA-MB-435 melanoma / None / Histology / 37.4±8.8 / 13.8±2.0 / QA / NQ / NQ
Intravital microscopy / 37.4±8.8 / 15.8±7.6 / QA / NQ / NQ
Sunitinib / Histology / 44.8±6.5 / 18.2±0.9 / QA / NQ / NQ
Control / Histology / 68.7±7.9 / 30.8±0.8 / QA / NQ / NQ
Mouse; EOMA hemangio-endothelioma / None / Histology / 60.3±9.6 / 28.7±6.9 / QA / NQ / NQ
Intravital microscopy / 60.3±9.6 / 16.4±8.1 / QA / NQ / NQ
*Not significantly different from MRI-based NmVD unless explicitly stated. ‡Average of cohorts of animals with either hypercarbia and hypocarbia at baseline.§SDnot reported and separate tumours used for MRI and validation studies (size matched).ǀǀTumour cores analysed.¤Median values and range. SD not reported.¶Conflictingdata or no match between MRI-derived vessel calibres and histologically derived calibres was obtained in this study. #Value estimated by us from data presented in a figure in the original publications.Abbreviations: BCNU, bischloroethylnitrosourea(carmustine); FM, fluorescence microscopy; LSM, laser scanning microscopy; MVD, microvessel density index; NmVD, normalized (tumour/reference tissue)mean vessel diameter; ND, no difference; NQ, not quantified; ρs, spearman rank correlation coefficient; QA, qualitative agreement; R2, linear regression descriptor ranging from 0 (no relationship) to 1 (perfect fit); SD, standard deviation; VSI, vessel size index.
References
S1. Dennie,J. et al. NMR imaging of changes in vascular morphology due to tumor angiogenesis. Magn Reson Med40, 793-799 (1998).
S2. Remy,C., Tropres,I., Péoc'h,M., Farion,R., & Decorps,M. In vivo NMR imaging of microvascularization in normal rat brain and in rat brain tumors. Proceedings of the 8th Annual Meeting of the International Society for Magnetic Resonance in Medicinep100, [Abstract] (2000).
S3. Badruddoja,M.A. et al. Antiangiogenic effects of dexamethasone in 9L gliosarcoma assessed by MRI cerebral blood volume maps. Neuro. Oncol5, 235-243 (2003).
S4. Packard,S.D. et al. Functional response of tumor vasculature to PaCO2: determination of total and microvascular blood volume by MRI. Neoplasia.5, 330-338 (2003).
S5. Robinson,S.P. et al. Tumor vascular architecture and function evaluated by non-invasive susceptibility MRI methods and immunohistochemistry. J Magn Reson. Imaging17, 445-454 (2003).
S6. Tropres,I. et al. In vivo assessment of tumoral angiogenesis. Magn Reson. Med.51, 533-541 (2004).
S7. Zwick,S. et al. Dynamic Contrast-Enhanced MRI and Vessel Size Imaging Sensitively Indicate Antiangiogenic Therapy Effects on Tumor Xenografts in Mice. Proceedings of the 15th Annual Meeting of the International Society for Magnetic Resonance in Medicinep564, [Abstract] (2007).
S8. Valable,S. et al. Assessment of blood volume, vessel size, and the expression of angiogenic factors in two rat glioma models: a longitudinal in vivo and ex vivo study. NMR Biomed.21, 1043-1056 (2008).
S9. Serduc,R. et al. Brain tumor vessel response to synchrotron microbeam radiation therapy: a short-term in vivo study. Phys. Med. Biol.53, 3609-3622 (2008).
S10. Robinson,S.P., Ludwig,C., Paulsson,J., & Ostman,A. The effects of tumor-derived platelet-derived growth factor on vascular morphology and function in vivo revealed by susceptibility MRI. Int. J Cancer122, 1548-1556 (2008).
S11. Beaumont,M. et al. Characterization of tumor angiogenesis in rat brain using iron-based vessel size index MRI in combination with gadolinium-based dynamic contrast-enhanced MRI. J. Cereb. Blood Flow Metab29, 1714-1726 (2009).
S12. Zwick,S. et al. Assessment of vascular remodeling under antiangiogenic therapy using DCE-MRI and vessel size imaging. J. Magn Reson Imaging29, 1125-1133 (2009).
S13. Yung,A.C. et al. Vessel Size Index and Blood Volume Imaging in Pancreatic Cancer Xenograft Model Using Ferumoxide. Proceedings of the 17th Annual Meeting of the International Society for Magnetic Resonance in Medicinep4227, [Abstract] (2009).
S14. Farrar,C.T. et al. In vivo validation of MRI vessel caliber index measurement methods with intravital optical microscopy in a U87 mouse brain tumor model. Neuro. Oncol.12, 341-350 (2010).
S15. Ungersma,S.E. et al. Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis. Magn Reson Med63, 1637-1647 (2010).
S16. Douma,K. et al. Evaluation of magnetic resonance vessel size imaging by two-photon laser scanning microscopy. Magn Reson. Med.63, 930-939 (2010).
S17. Bauerle,T., Merz,M., Komljenovic,D., Zwick,S., & Semmler,W. Drug-induced vessel remodeling in bone metastases as assessed by dynamic contrast enhanced magnetic resonance imaging and vessel size imaging: a longitudinal in vivo study. Clin. Cancer Res.16, 3215-3225 (2010).
S18. Merz,M., Komljenovic,D., Zwick,S., Semmler,W., & Bauerle,T. Sorafenib tosylate and paclitaxel induce anti-angiogenic, anti-tumour and anti-resorptive effects in experimental breast cancer bone metastases. Eur. J Cancer47, 277-286 (2011).
S19. Ullrich,R.T. et al. In-vivo visualization of tumor microvessel density and response to anti-angiogenic treatment by high resolution MRI in mice. PLoS. One.6, e19592 (2011).
S20. Lemasson,B. et al. Assessment of multiparametric MRI in a human glioma model to monitor cytotoxic and anti-angiogenic drug effects. NMR Biomed.24, 473-482 (2011).
S21. Yuan,A. et al. Functional and structural characteristics of tumor angiogenesis in lung cancers overexpressing different VEGF isoforms assessed by DCE- and SSCE-MRI. PLoS. One.6, e16062 (2011).
S22. Just,N. Histogram analysis of the microvasculature of intracerebral human and murine glioma xenografts. Magn Reson. Med.65, 778-789 (2011).
S23. Remmele,S. et al. Concurrent MR blood volume and vessel size estimation in tumors by robust and simultaneous DeltaR2 and DeltaR2* quantification. Magn Reson. Med.66, 144-153 (2011).
S24. Wyatt,S.K. et al. Dual PI3K/mTOR Inhibition Induces Structural Changes in Tumor Vasculature Assessed by Vessel Size Imaging. Proceedings of the 19th Annual Meeting of the International Society for Magnetic Resonance in Medicinep556, [Abstract] (2011).
S25. Nielsen,T. et al. Combretastatin A-4 phosphate affects tumor vessel volume and size distribution as assessed using MRI-based vessel size imaging. Clin. Cancer Res.18, 6469-6477 (2012).
S26. Walker-Samuel,S. et al. Non-invasive in vivo imaging of vessel calibre in orthotopic prostate tumour xenografts. Int. J Cancer130, 1284-1293 (2012).
S27. Burrell,J.S. et al. MRI measurements of vessel calibre in tumour xenografts: comparison with vascular corrosion casting. Microvasc. Res.84, 323-329 (2012).
S28. Jin,N., Guo,Y., Klein,R., & Larson,A.C. MR Vessel imaging for Tumor Angiogenesis Quantification in Two Rodent Models of Hepatocellular Carcinoma. Proceedings of the 20th Annual Meeting of the International Society for Magnetic Resonance in Medicinep3018, [Abstract] (2012).
S29. Boult,J.K. et al. False-negative MRI biomarkers of tumour response to targeted cancer therapeutics. Br. J Cancer106, 1960-1966 (2012).
S30. Kim,E. et al. Assessing breast cancer angiogenesis in vivo: which susceptibility contrast MRI biomarkers are relevant? Magn Reson. Med.70, 1106-1116 (2013).
S31. Lemasson,B. et al. In vivo imaging of vessel diameter, size, and density: a comparative study between MRI and histology. Magn Reson. Med.69, 18-26 (2013).
S32. Boult,J.K., Terkelsen,J., Walker-Samuel,S., Bradley,D.P., & Robinson,S.P. A multi-parametric imaging investigation of the response of C6 glioma xenografts to MLN0518 (tandutinib) treatment. PLoS. One.8, e63024 (2013).
S33. Viel,T. et al. Non-invasive imaging of glioma vessel size and densities in correlation with tumour cell proliferation by small animal PET and MRI. Eur. J. Nucl. Med. Mol. Imaging40, 1595-1606 (2013).
S34. Persigehl,T. et al. Vessel Size Imaging (VSI) by Robust Magnetic Resonance (MR) Relaxometry: MR-VSI of Solid Tumors in Correlation with Immunohistology and Intravital Microscopy. Mol. Imaging12, 1-11 (2013).