[Show abstract][Hide abstract] ABSTRACT: 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).
PLoS ONE 10/2014; 9(10):e108052. · 3.53 Impact Factor
[Show abstract][Hide abstract] 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. · 0.80 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Respiratory motion commonly confounds abdominal DWI, and motion minimisation strategies adversely affect scan efficiency and comfort. Blurring is due to post-acquisition combination of images from separate signal averages and diffusion-gradient directions, and is not inherent to the images. In a volunteer cohort where all images were stored separately, taking a (voxel-by-voxel) median image instead of a mean at each b-value yields parameter maps with much improved sharpness while still retaining tissue features. ADCs from ROIs in liver and kidneys were 108±18 vs 120±26 (p=0.007) and 182±17 vs 188±13 (p=0.04) x10-5 mm2s-1 for median and mean, respectively.
[Show abstract][Hide abstract] ABSTRACT: In this article, we review recent updates in the deployment of diffusion weighted magnetic resonance imaging (DW-MRI) in oncology for disease detection and characterization. We appraise the use of DW-MRI for the evaluation of treatment response, including its emerging role as a predictive and/or prognostic biomarker. We discuss the use of more sophisticated data analysis to derive quantitative parameters, particular those that account for non-mono-exponential signal attenuation behavior of DW-MRI in tissues. Last but not least, we survey the unfulfilled challenges and potential future applications of DW-MRI. Knowledge of the fundamentals of DW-MRI is assumed and will not be discussed.
[Show abstract][Hide abstract] ABSTRACT: We describe our semi-automatic segmentation of whole-body diffusion-weighted MRI (WBDWI) using a Markov random field (MRF) model to derive tumor total diffusion volume (tDV) and associated global apparent diffusion coefficient (gADC); and demonstrate the feasibility of using these indices for assessing tumor burden and response to treatment in patients with bone metastases. WBDWI was performed on eleven patients diagnosed with bone metastases from breast and prostate cancers before and after anti-cancer therapies. Semi-automatic segmentation incorporating a MRF model was performed in all patients below the C4 vertebra by an experienced radiologist with over eight years of clinical experience in body DWI. Changes in tDV and gADC distributions were compared with overall response determined by all imaging, tumor markers and clinical findings at serial follow up. The segmentation technique was possible in all patients although erroneous volumes of interest were generated in one patient because of poor fat suppression in the pelvis, requiring manual correction. Responding patients showed a larger increase in gADC (median change = +0.18, range = -0.07 to +0.78×10-3 mm2/s) after treatment compared to non-responding patients (median change = -0.02, range = -0.10 to +0.05×10-3 mm2/s, p = 0.05, Mann-Whitney test), whereas non-responding patients showed a significantly larger increase in tDV (median change = +26%, range = +3 to +284%) compared to responding patients (median change = -50%, range = -85 to +27%, p = 0.02, Mann-Whitney test). Semi-automatic segmentation of WBDWI is feasible for metastatic bone disease in this pilot cohort of 11 patients, and could be used to quantify tumor total diffusion volume and median global ADC for assessing response to treatment.
PLoS ONE 04/2014; 9(4):e91779. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The early identification of children presenting ALKF1174L-mutated neuroblastoma, which are associated with resistance to the promising ALK inhibitor crizotinib and a marked poorer prognosis, has become a clinical priority. In comparing the radiology of the novel Th-ALKF1174L/Th-MYCN and the well-established Th-MYCN genetically-engineered murine models of neuroblastoma using MRI, we have identified a marked ALKF1174L-driven vascular phenotype. We demonstrate that quantitation of the transverse relaxation rate R2* (s-1) using intrinsic susceptibility-MRI under baseline conditions and during hyperoxia, can robustly discriminate this differential vascular phenotype, and identify MYCN-driven tumors harboring the ALKF1174L mutation with high specificity and selectivity. Intrinsic susceptibility-MRI could thus potentially provide a non-invasive and clinically-exploitable method to help identifying children with MYCN-driven neuroblastoma harboring the ALKF1174L mutation at the time of diagnosis.
PLoS ONE 03/2014; 9(3):e92886. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autophagy is a highly regulated, energy dependent cellular process where proteins, organelles and cytoplasm are sequestered in autophagosomes and digested to sustain cellular homeostasis. We hypothesized that during autophagy induced in cancer cells by i) starvation through serum and amino acid deprivation or ii) treatment with PI-103, a class I PI3K/mTOR inhibitor, glycolytic metabolism would be affected, reducing flux to lactate, and that this effect may be reversible. We probed metabolism during autophagy in colorectal HT29 and HCT116 Bax knock-out cells using hyperpolarized 13C-magnetic resonance spectroscopy (MRS) and steady-state 1H-MRS. 24 hr PI103-treatment or starvation caused significant reduction in the apparent forward rate constant (kPL) for pyruvate to lactate exchange compared with controls in HT29 (100 μM PI-103: 82%, p = 0.05) and HCT116 Bax-ko cells (10 μM PI-103: 53%, p = 0.05; 20 μM PI-103: 42%, p<0.0001; starvation: 52%, p<0.001), associated with reduced lactate excretion and intracellular lactate in all cases, and unchanged lactate dehydrogenase (LDH) activity and increased NAD+/NADH ratio following PI103 treatment or decreased LDH activity and unchanged NAD+/NADH ratio following starvation. After 48 hr recovery from PI103 treatment, kPL remained below control levels in HT29 cells (74%, p = 0.02), and increased above treated values, but remained below 24 hr vehicle-treated control levels in HCT116 Bax-ko cells (65%, p = 0.004) both were accompanied by sustained reduction in lactate excretion, recovery of NAD+/NADH ratio and intracellular lactate. Following recovery from starvation, kPL was significantly higher than 24 hr vehicle-treated controls (140%, p = 0.05), associated with increased LDH activity and total cellular NAD(H). Changes in kPL and cellular and excreted lactate provided measureable indicators of the major metabolic processes accompanying starvation- and drug-induced autophagy. The changes are reversible, returning towards and exceeding control values on cellular recovery, which potentially identifies resistance. kPL (hyperpolarized 13C-MRS) and lactate (1H-MRS) provide useful biomarkers for the autophagic process, enabling non-invasive monitoring of the Warburg effect.
PLoS ONE 03/2014; 9(3):e92645. · 3.53 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE
To determine the prognostic value of pretreatment ADC of colorectal liver metastases in predicting disease response, progression free survival (PFS) and overall survival (OS).
METHOD AND MATERIALS
We retrospectively reviewed 109 patients with colorectal liver metastasis who underwent pretreatment DW-MRI using breath-hold (b=0, 150, 500) or free-breathing (b=0, 50, 100, 250, 500, 750) technique. The mean ADC (b=0 to 500) and mean ADChigh values (breath-hold: b=150 and 500; free-breathing: b=100 and 500) of up to 3 hepatic lesions were evaluated in each patient. Clinical and laboratory parameters were recorded. Tumor response was assessed by RECIST criteria at 12 weeks after treatment. Associations between tumor response, ADC values and clinical/laboratory parameters were examined by one-way ANOVA. The relationship of ADC with PFS and OS were determined by Kaplan-Meier analysis.
The final study cohort consisted of 102 patients after the exclusion of 7 patients on the basis of previous or concurrent non-colorectal cancer. 62 patients responded to chemotherapy at 12 weeks. The pretreatment mean ADC and mean ADChigh were higher in the non-responding group than the responding group (1.55 vs 1.36 x 10-3 mm2/s; p=0.033; 1.40 vs 1.16 x 10-3 mm2/s; p=0.024). When patients were dichotomised by the median ADChigh value of 1.13 x 10-3 mm2/s, the proportion of non-responders below this value was 0.3, whereas proportion of non-responders above this value was 0.43; odds ratio 1.73. The PFS and OS of the 2 groups of patients dichotomised by median of mean ADC values or threshold derived by receiver operating characteristic analysis were not statistically significant. By multivariate Cox regression analysis, patients with ≤2 metastases and response to chemotherapy showed better PFS (hazard ratios of 0.540 and 0.360; p = 0.022 and <0.001 respectively); white cell count ≤10 and surgical treatment were associated with better OS (hazard ratios of 0.287 and 0.163; p = 0.023 and 0.001).
Colorectal liver metastasis with higher pre-treatment mean ADC and mean ADChigh were associated with poorer response to chemotherapy. However, ADC and ADChigh values did not predict patient outcome in this study cohort.
ADC derived from DW-MRI may be used to predict treatment response in colorectal liver metastasis.
The British journal of radiology 08/2013; 86(1030). · 2.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diffusion-weighted MRI in the body must account for a microcirculation fraction, separate to self-diffusion, within imaging voxels. Explicit control of diffusion pulse length and delay allows reproducible application of diffusion gradients with varying echo times; calculation of mono-exponential T2 estimates with applied gradients of b=0 and b=200 s/mm2 shows significant changes observed in liver, kidney and spleen. This suggests that the microcirculation component, with its own distinct T2, is being removed, allowing the generation of flow-free T2 maps more robustly estimating tissue T2s. This approach enables appropriate b-value choices when considering diffusion models that include or exclude microcirculation contribution.
ISMRM Annual Meeting & Exhibition, Salt Lake City, Utah, USA; 04/2013
[Show abstract][Hide abstract] ABSTRACT: Liver-specific magnetic resonance (MR) contrast agents are increasingly used in evaluation of the liver. They are effective in detection and morphological characterization of lesions, and can be useful for evaluation of biliary tree anatomy and liver function. The typical appearances and imaging pitfalls of various tumours at MR imaging performed with these agents can be understood by the interplay of pharmacokinetics of these contrast agents and transporter expression of the tumour. This review focuses on the applications of these agents in oncological imaging.
Cancer Imaging 01/2013; 13(4):567-79. · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diffusion-weighted magnetic resonance (MR) imaging (DWI) is now widely incorporated as a standard MR imaging sequence for the assessment of the male pelvis. DWI can improve the detection, characterization, and staging of pelvic malignancies, such as prostate, bladder, and rectal cancers. There is growing interest in applying quantitative DWI for the assessment of tumor treatment response. In addition, the technique seems promising for the evaluation of metastatic nodal and bone disease in the pelvis.
Radiologic Clinics of North America 11/2012; 50(6):1127-44. · 1.83 Impact Factor