Dow-Mu Koh

Institute of Cancer Research, Londinium, England, United Kingdom

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Publications (91)263.71 Total impact

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    ABSTRACT: To evaluate non-invasive imaging biomarkers for assessing renal fibrosis. DWI is used to assess renal function, intravoxel incoherent motion (IVIM) provides additional measures of perfusion-related diffusion (D*-blood flow, f-perfusion fraction). We aim to determine if reduced ADC seen in renal fibrosis is attributable to perfusion-related diffusion changes or to known reduction in tissue diffusivity (D). Unilateral ureteral obstruction (UUO) was created in six mice to induce renal fibrosis. DWI was performed the day before and 7 days post-UUO. A range of b-values from 0 to 1200 s/mm(2) were used. IVIM parameters were obtained using region of interests drawn over the renal parenchyma. Histopathological analysis of both kidneys were performed in all mice. Results were analysed using the paired t-test with P<0.05 considered statistically significant. D and f was significantly lower in the ligated kidneys at Day 7 compared to before ligation and no significant difference was found for D*. Comparing non-ligated and ligated kidneys within the same mouse at Day 7, significantly lower D values were observed in the ligated kidneys, while no significant difference was found for f and D*, although the values of f were generally lower. Histopathological analysis confirmed development of fibrosis and reduction in glomeruli in all the ligated kidneys at Day 7. Our study shows that the reduction in ADC seen in renal fibrosis is attributable not only to reduced D as previously encountered but also a decrease in vascularity as assessed by f. Reduction in f is possibly related to a reduction in glomeruli. Copyright © 2015. Published by Elsevier Inc.
    Magnetic Resonance Imaging 08/2015; DOI:10.1016/j.mri.2015.07.012 · 2.02 Impact Factor
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    ABSTRACT: Technologic advances enable performance of diffusion-weighted imaging (DWI) at ultrahigh b-values, where standard monoexponential model analysis may not apply. Rather, non-Gaussian water diffusion properties emerge, which in cellular tissues are, in part, influenced by the intracellular environment that is not well evaluated by conventional DWI. The novel technique, diffusion kurtosis imaging (DKI), enables characterization of non-Gaussian water diffusion behavior. More advanced mathematical curve fitting of the signal intensity decay curve using the DKI model provides an additional parameter Kapp that presumably reflects heterogeneity and irregularity of cellular microstructure, as well as the amount of interfaces within cellular tissues. Although largely applied for neural applications over the past decade, a small number of studies have recently explored DKI outside the brain. The most investigated organ is the prostate, with preliminary studies suggesting improved tumor detection and grading using DKI. Although still largely in the research phase, DKI is being explored in wider clinical settings. When assessing extracranial applications of DKI, careful attention to details with which body radiologists may currently be unfamiliar is important to ensure reliable results. Accordingly, a robust understanding of DKI is necessary for radiologists to better understand the meaning of DKI-derived metrics in the context of different tumors and how these metrics vary between tumor types and in response to treatment. In this review, we outline DKI principles, propose biostructural basis for observations, provide a comparison with standard monoexponential fitting and the apparent diffusion coefficient, report on extracranial clinical investigations to date, and recommend technical considerations for implementation in body imaging. J. Magn. Reson. Imaging 2015. © 2015 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 06/2015; DOI:10.1002/jmri.24985 · 2.79 Impact Factor
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    ABSTRACT: Cancer is the leading cause of death in children older than 1 year of age and new drugs are necessary to improve outcomes. Imaging is crucial to the drug development process and assessment of therapeutic response. In adults, tumours are often assessed with CT using size criteria. Unfortunately, techniques established in adults are not necessarily applicable in children due to differing pathophysiology, ability to cooperate and increased susceptibility to ionising radiation. MRI, in particular quantitative MRI, has to date not been fully utilised in children with extracranial neoplasms. The specific challenges of imaging in children, the potential for functional imaging techniques to inform upon and their inclusion in clinical trials are discussed.
    Pediatric Radiology 06/2015; DOI:10.1007/s00247-015-3342-8 · 1.65 Impact Factor
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    ABSTRACT: Radical chemo-radiotherapy (CRT) is an effective organ-sparing treatment option for patients with locally advanced head and neck cancer (LAHNC). Despite advances in treatment for LAHNC, a significant minority of these patients continue to fail to achieve complete response with standard CRT. By constructing a multi-modality functional imaging (FI) predictive biomarker for CRT outcome for patients with LAHNC we hope to be able to reliably identify those patients at high risk of failing standard CRT. Such a biomarker would in future enable CRT to be tailored to the specific biological characteristics of each patients' tumour, potentially leading to improved treatment outcomes. The INSIGHT study is a single-centre, prospective, longitudinal multi-modality imaging study using functional MRI and FDG-PET/CT for patients with LAHNC squamous cell carcinomas receiving radical CRT. Two cohorts of patients are being recruited: one treated with, and another treated without, induction chemotherapy. All patients receive radical intensity modulated radiotherapy with concurrent chemotherapy. Patients undergo functional imaging before, during and 3 months after completion of radiotherapy, as well as at the time of relapse, should that occur within the first two years after treatment. Serum samples are collected from patients at the same time points as the FI scans for analysis of a panel of serum markers of tumour hypoxia. The primary aim of the INSIGHT study is to acquire a prospective multi-parametric longitudinal data set comprising functional MRI, FDG PET/CT, and serum biomarker data from patients with LAHNC undergoing primary radical CRT. This data set will be used to construct a predictive imaging biomarker for outcome after CRT for LAHNC. This predictive imaging biomarker will be used in future studies of functional imaging based treatment stratification for patients with LAHNC. Additional objectives are: defining the reproducibility of FI parameters; determining robust methods for defining FI based biological target volumes for IMRT planning; creation of a searchable database of functional imaging data for data mining. The INSIGHT study will help to establish the role of FI in the clinical management of LAHNC. NCRI H&N CSG ID 13860.
    Radiation Oncology 05/2015; 10(1):112. DOI:10.1186/s13014-015-0415-7 · 2.36 Impact Factor
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    ABSTRACT: Background To evaluate diffusion-weighted MR neurography (DW-MRN) for visualizing the brachial plexus and for the assessment of brachial plexopathy. Methods 40 oncological patients with symptoms of brachial plexopathy underwent 1.5 T MRI using conventional MR sequences and unidirectional DW-MRN. The images were independently reviewed by two radiologists. Anatomic visualization of the brachial plexus was scored using a 5 point scale on conventional MR sequences and then combined with DW-MRN. A brachial plexus abnormality was also scored using a 5 point scale and inter-observer agreement determined by kappa statistics. Diagnostic accuracy for brachial plexopathy assessed by conventional MRI alone versus conventional MRI combined with DW-MRN was compared by ROC analysis using reference standards. Results DW-MRN significantly improved visualization of the brachial plexus compared with conventional MRI alone (P < 0.001). When assessing brachial plexopathy, inter-observer agreement was moderate for conventional MRI (kappa = 0.48) but good for conventional MRI with DW-MRN (kappa = 0.62). DW-MRN combined with conventional MRI significantly improved diagnostic accuracy in one observer (P < 0.05) but was similar in the other observer. Conclusion DW-MRN improved visualization of the brachial plexus. Combining DW-MRN with conventional MRI can improve inter-observer agreement and detection of brachial plexopathy in symptomatic oncological patients.
    Cancer imaging : the official publication of the International Cancer Imaging Society 05/2015; 15(1). DOI:10.1186/s40644-015-0041-5 · 1.29 Impact Factor
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    ABSTRACT: This open-label phase I dose-escalation study investigated the safety, efficacy, pharmacokinetics (PK), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) effects of the oral angiokinase inhibitor nintedanib in patients with advanced solid tumors. Nintedanib was administered once daily continuously, starting at 100 mg and later amended to allow evaluation of 250 mg b.i.d. The primary endpoint was maximum tolerated dose (MTD). DCE-MRI studies were performed at baseline and on days 2 and 28. Fifty-one patients received nintedanib 100-450 mg once daily (n = 40) or 250 mg b.i.d. (n = 11). Asymptomatic reversible liver enzyme elevations (grade 3) were dose limiting in 2 of 5 patients at 450 mg once daily. At 250 mg b.i.d., 2 of 11 patients experienced dose-limiting toxicity (grade 3 liver enzyme elevation and gastrointestinal symptoms). Common toxicities included fatigue, diarrhea, nausea, vomiting, and abdominal pain (mainly grade ≤2). Among 45 patients, 22 (49%) achieved stable disease; 7 remained on treatment for >6 months. DCE-MRI of target lesions revealed effects in some patients at 200 and ≥400 mg once daily. Nintedanib is well tolerated by patients with advanced solid malignancies, with MTD defined as 250 mg b.i.d., and can induce changes in DCE-MRI. Disease stabilization >6 months was observed in 7 of 51 patients. ©AlphaMed Press; the data published online to support this summary is the property of the authors.
    The Oncologist 03/2015; 20(4). DOI:10.1634/theoncologist.2014-0250 · 4.54 Impact Factor
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    ABSTRACT: Contrast-Enhanced Magnetic Resonance Lymphangiography (CE-MRL) presents some limitations: (i) it does not quantify lymphatic functionality; and (ii) enhancement of vascular structures may confound image interpretation. Furthermore, although CE-MRL is well described in the published literature for the lower limbs, there is a paucity of data with regards to its use in the upper limbs. In this proof-of-principle study, we propose a new protocol to perform CE-MRL in the upper limbs of patients with breast cancer-related lymphedema (BCRL) which addresses these limitations. CE-MRL was performed using a previously published (morphological) protocol and the proposed protocol (quantitative) on both the ipsilateral (abnormal) and contralateral (normal) arms of patients with BCRL. The quantitative protocol employs contrast agent (CA) intradermal injections at a lower concentration to prevent T2*-related signal decay. Both protocols provided high-resolution three-dimensional images of upper limb lymphatic vessels. CA uptake curves were utilized to distinguish between lymphatic vessels and vascular structures. The quantitative protocol minimized venous enhancement and avoided spurious delays in lymphatic enhancement due to short T2* values, enabling correct CA uptake characterization. The quantitative protocol was therefore employed to measure the lymphatic fluid velocity, which demonstrated functional differences between abnormal and normal arms. The velocity values were in agreement with previously reported lymphoscintigraphy and near infra-red lymphangiography measurements. This work demonstrated the feasibility of CE-MRL of the upper limbs in patients with BRCL, introducing an advanced imaging and analysis protocol suitable for anatomical and functional study of the lymphatic system.
    Lymphatic Research and Biology 03/2015; 13(2). DOI:10.1089/lrb.2014.0039 · 1.66 Impact Factor
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    ABSTRACT: The objectives are to examine the reproducibility of functional MR imaging in children with solid tumours using quantitative parameters derived from diffusion-weighted (DW-) and dynamic contrast enhanced (DCE-) MRI. Patients under 16-years-of age with confirmed diagnosis of solid tumours (n = 17) underwent free-breathing DW-MRI and DCE-MRI on a 1.5 T system, repeated 24 hours later. DW-MRI (6 b-values, 0-1000 sec/mm(2)) enabled monoexponential apparent diffusion coefficient estimation using all (ADC0-1000) and only ≥100 sec/mm(2) (ADC100-1000) b-values. DCE-MRI was used to derive the transfer constant (K(trans)), the efflux constant (kep), the extracellular extravascular volume (ve), and the plasma fraction (vp), using a study cohort arterial input function (AIF) and the extended Tofts model. Initial area under the gadolinium enhancement curve and pre-contrast T1 were also calculated. Percentage coefficients of variation (CV) of all parameters were calculated. The most reproducible cohort parameters were ADC100-1000 (CV = 3.26 %), pre-contrast T1 (CV = 6.21 %), and K(trans) (CV = 15.23 %). The ADC100-1000 was more reproducible than ADC0-1000, especially extracranially (CV = 2.40 % vs. 2.78 %). The AIF (n = 9) derived from this paediatric population exhibited sharper and earlier first-pass and recirculation peaks compared with the literature's adult population average. Free-breathing functional imaging protocols including DW-MRI and DCE-MRI are well-tolerated in children aged 6 - 15 with good to moderate measurement reproducibility. • Diffusion MRI protocol is feasible and well-tolerated in a paediatric oncology population. • DCE-MRI for pharmacokinetic evaluation is feasible and well tolerated in a paediatric oncology population. • Paediatric arterial input function (AIF) shows systematic differences from the adult population-average AIF. • Variation of quantitative parameters from paired functional MRI measurements were within 20 %.
    European Radiology 03/2015; DOI:10.1007/s00330-015-3666-7 · 4.34 Impact Factor
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    ABSTRACT: Angiogenesis is a key cancer hallmark involved in tumor growth and metastasis development. Angiogenesis and tumor microenvironment significantly influence the response of tumors to therapies. Imaging techniques have changed our understanding of the process of angiogenesis, the resulting vascular performance, and the tumor microenvironment. This article reviews the status and potential clinical value of the imaging modalities used to assess the status of tumor vasculature in vivo, before, during, and after treatment. Copyright © 2015 Mosby, Inc. All rights reserved.
    Current problems in diagnostic radiology 03/2015; DOI:10.1067/j.cpradiol.2015.02.009
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    ABSTRACT: Angiogenesis is a key cancer hallmark involved in tumor growth and metastasis development. Tumor angiogenesis is the process whereby new blood vessels are formed to supply nutrients and oxygen to support the growth of tumors. This article reviews the biological basis behind imaging features and the different imaging modalities used to assess the status of tumor neovasculature in vivo at different scales: structural, functional, and molecular. Copyright © 2015 Mosby, Inc. All rights reserved.
    Current problems in diagnostic radiology 03/2015; DOI:10.1067/j.cpradiol.2015.02.010
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    ABSTRACT: The aim of this study was to determine the value of SUV-based metabolic parameters derived from pretreatment F-FDG PET/CT of colorectal liver metastases in predicting disease response, progression-free survival (PFS), and overall survival (OS). We retrospectively reviewed 70 colorectal patients with liver metastases who underwent pretreatment F-FDG PET/CT. SUVmean, SUVmax, TLG (total lesion glycolysis), metabolic tumor volume, and metabolic tumor diameter were the metabolic parameters derived from volume of interest analysis of the most FDG-avid liver lesion in each subject. Clinical and laboratory parameters were recorded. Tumor response was assessed by response evaluation criteria in solid tumors 1.1 criteria at 12 weeks after treatment. Associations between tumor response, metabolic parameters, and clinical/laboratory parameters were examined by 1-way analysis of variance. The relationship of the metabolic parameters with PFS and OS was determined by Kaplan-Meier analyses and further confirmed with multivariate Cox regression analyses. SUVmean less than 4.48, SUVmax less than 6.59, TLG less than 75.2, metabolic tumor volume less than 4.49 cm, and hemoglobin level greater than or equal to 11 g/dL were associated with longer PFS (P < 0.05). Prior surgery or radiofrequency ablation to the liver metastases was the only additional factor shown to be associated with longer OS. SUV-based metabolic parameters derived from pretreatment F-FDG PET/CT can predict PFS in colorectal liver metastases.
    Clinical Nuclear Medicine 02/2015; 40(5). DOI:10.1097/RLU.0000000000000744 · 2.86 Impact Factor
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  • Anwar Padhani · Dow-Mu Koh
    Cancer imaging : the official publication of the International Cancer Imaging Society 10/2014; 14(Suppl 1):O47-O47. DOI:10.1186/1470-7330-14-S1-O47 · 1.29 Impact Factor
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    ABSTRACT: Objective The aim of this study was to prospectively evaluate the feasibility of monitoring treatment response to chemotherapy in patients with non-small cell lung carcinoma using functional diffusion maps (fDMs). Materials and Methods This study was approved by the Cantonal Research Ethics Committee and informed written consent was obtained from all patients. Nine patients (mean age = 66 years; range = 53–76 years, 5 females, 4 males) with overall 13 lesions were included. Imaging was performed within two weeks before initiation of chemotherapy and at one, two, and six weeks after initiation of chemotherapy. Imaging included a respiratory-triggered diffusion-weighted sequence including three b-factors (100, 600, and 800 s/mm2). Treatment response was defined by change in tumor diameter on computed tomography (CT) after two cycles of chemotherapy. Changes in the apparent diffusion coefficient (ADC) on a per-lesion basis and the percentages of voxel with significantly increased or decreased ADCs on fDMs were analyzed using repeated measures analysis of variance (ANOVA). Changes in tumor size were used as covariate to examine the ability of ADCs and fDM parameters to predict treatment response. Results Repeated measures ANOVA revealed that the percentage of voxels with increased ADCs on fDMs (p = 0.002) as well as the mean ADC increase (p = 0.011) were significantly higher in good responders with a large reduction in tumor size on CT. Conclusion Our results indicate that the percentage of voxels with significantly increased ADCs on fDMs seems to be a promising biomarker for early prediction of treatment response in patients with non-small cell lung carcinoma. Contrary to averaged values, this approach allows the spatial heterogeneity of treatment response to be resolved.
    PLoS ONE 10/2014; 9(10):e108052. DOI:10.1371/journal.pone.0108052 · 3.23 Impact Factor
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    ABSTRACT: Liver perfusion magnetic resonance (MR) imaging is currently being actively investigated as a functional imaging technique that provides physiologic information on the microcirculation and microenvironment of liver tumors and the underlying liver. It has gained importance in light of antiangiogenic therapy for hepatocellular carcinoma and colorectal liver metastases. This article explains the various model-free and model-based approaches for liver perfusion MR imaging and their relative clinical utility. Relevant published works are summarized for each approach so that the reader can understand their relative strengths and weaknesses, to make an informed choice when performing liver perfusion MR imaging studies.
    Magnetic Resonance Imaging Clinics of North America 08/2014; 22(3):417–432. DOI:10.1016/j.mric.2014.04.011 · 0.80 Impact Factor
  • Dow-Mu Koh
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    ABSTRACT: Summary In the study by Joo et al ( 1 ), perfusion-sensitive parameters derived from diffusion-weighted (DW) magnetic resonance (MR) imaging using intravoxel incoherent motion (IVIM) analysis were significantly decreased 4 hours after administration of a vascular disrupting agent (VDA) (CKD-516), in keeping with drug-induced vascular collapse. A larger decrease in the perfusion-sensitive IVIM parameters was correlated with smaller tumor size increase 7 days after treatment.
    Radiology 08/2014; 272(2):307-308. DOI:10.1148/radiol.14140714 · 6.21 Impact Factor
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    ABSTRACT: BACKGROUND: Dichloroacetate (DCA) has been found to have antitumour properties. METHODS: We investigated the cellular and metabolic responses to DCA treatment and recovery in human colorectal (HT29, HCT116 WT and HCT116 Bax-ko), prostate carcinoma cells (PC3) and HT29 xenografts by flow cytometry, western blotting, electron microscopy, (1)H and hyperpolarised (13)C-magnetic resonance spectroscopy. RESULTS: Increased expression of the autophagy markers LC3B II was observed following DCA treatment both in vitro and in vivo. We observed increased production of reactive oxygen species (ROS) and mTOR inhibition (decreased pS6 ribosomal protein and p4E-BP1 expression) as well as increased expression of MCT1 following DCA treatment. Steady-state lactate excretion and the apparent hyperpolarised [1-(13)C] pyruvate-to-lactate exchange rate (kPL) were decreased in DCA-treated cells, along with increased NAD(+)/NADH ratios and NAD(+). Steady-state lactate excretion and kPL returned to, or exceeded, control levels in cells recovered from DCA treatment, accompanied by increased NAD(+) and NADH. Reduced kPL with DCA treatment was found in HT29 tumour xenografts in vivo. CONCLUSIONS: DCA induces autophagy in cancer cells accompanied by ROS production and mTOR inhibition, reduced lactate excretion, reduced kPL and increased NAD(+)/NADH ratio. The observed cellular and metabolic changes recover on cessation of treatment.
    British Journal of Cancer 07/2014; 111(2). DOI:10.1038/bjc.2014.281 · 4.82 Impact Factor
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    ABSTRACT: Purpose To compare revised Choi criteria that incorporate concurrent size and attenuation changes at early follow-up imaging with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and original Choi criteria in stratification of clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib. Materials and Methods Institutional review board approved this retrospective study and waived informed consent. Baseline and first follow-up computed tomographic scans in 69 patients (50 men, 19 women; mean age, 60.3 years; range, 19-83 years) with mRCC treated with sunitinib from October 1, 2008, to March 1, 2013, were evaluated for tumor response by using RECIST 1.1, original Choi criteria, and revised Choi criteria. Correlations with overall survival (OS) and progression-free survival (PFS) were compared and stratified according to each radiologic criteria with Kaplan-Meier and multivariate Cox regression analysis. Results Median follow-up time was 29.7 months (95% confidence interval [CI]: 18.9, 45.9). Response according to revised Choi criteria was independently correlated with OS (hazard ratio, 0.47 [95% CI: 0.23, 0.99]; P = .046) and PFS (hazard ratio, 0.53 [95% CI: 0.29, 0.99]; P = .047). Response according to RECIST was not significantly correlated with OS (hazard ratio, 0.65 [95% CI: 0.27, 1.58]; P = .344) or PFS (hazard ratio, 0.89 [95% CI: 0.42, 1.91]; P = .768). Response according to original Choi criteria was not significantly correlated with OS (hazard ratio, 0.60 [95% CI: 0.32, 1.11]; P = .106) or PFS (hazard ratio, 0.59 [95% CI: 0.34, 1.02]; P = .060). Median OS and PFS in responders according to revised Choi criteria was 39.4 months (95% CI: 9.1, upper limit not estimated) and 13.7 months (95% CI: 6.4, 24.6), respectively, compared with 12.8 months (95% CI: 8.7, 18.0) and 5.3 months (95% CI: 3.9, 8.4), respectively, in nonresponders. Conclusion Contemporaneous reduction in tumor size and attenuation were correlated with favorable clinical outcomes. Response according to revised Choi criteria showed better correlation with clinical outcomes compared with that according to RECIST or original Choi criteria in patients with mRCC treated with sunitinib. © RSNA, 2014.
    Radiology 05/2014; 273(2):132702. DOI:10.1148/radiol.14132702 · 6.21 Impact Factor
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    ABSTRACT: We investigated how the technical differences between ss-EPI(R=2), FLASH(R=2) and FLASH(R=3) ACS acquisition methods visually manifest themselves in the context of WBDWI imaging. We analyzed: geometric distortion, SNR, overall image quality, and inter-station registration. FLASH(R=3) had the highest geometric fidelity, fewer image artifacts, and good station-station alignment. These advantages are offset by a lower SNR of ~17%: this may be partially responsible for the tendency of FLASH(R=2) ACS data to be rated higher than FLASH(R = 3) ACS data in terms of overall MIP quality. There was no situation in this study in which ss-EPI outperformed FLASH.
    Joint Annual Meeting ISMRM-ESMRMB, Milan, Italy; 05/2014
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    ABSTRACT: The intra-voxel incoherent motion (IVIM) model relates signal decay on diffusion-weighted MRI (DWI) to tissue characteristics of perfusion and diffusivity. We explored the effects of altering the diffusion time of DWI sequences on IVIM perfusion (f,D*) and diffusion (D) related parameters in abdominal organs of healthy volunteers. At longer diffusion times, the calculated perfusion fraction (f) was significantly increased while the effect on the D and D* parameters was more variable, depending on the organ under study. The diffusion time has a significant impact on measured IVIM parameters in abdominal organs and should be reported when employing the IVIM model.
    Joint Annual Meeting ISMRM-ESMRMB, Milan, Italy; 05/2014

Publication Stats

2k Citations
263.71 Total Impact Points

Institutions

  • 2008–2015
    • Institute of Cancer Research
      • CR-UK and EPSRC Cancer Imaging Centre
      Londinium, England, United Kingdom
  • 2012–2014
    • Ontario Institute for Cancer Research
      Toronto, Ontario, Canada
  • 2008–2014
    • The Royal Marsden NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2009
    • University of Michigan
      Ann Arbor, Michigan, United States
    • Johns Hopkins Medicine
      • Department of Radiology and Radiological Science
      Baltimore, MD, United States
    • NYU Langone Medical Center
      • Department of Radiology
      New York City, NY, United States