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1.
Nat Sci Sleep ; 12: 69-78, 2020.
Article in English | MEDLINE | ID: mdl-32095087

ABSTRACT

PURPOSE: An increasing number of studies have linked the severity of obstructive sleep apnea (OSA) with metabolic dysfunction. However, little is known about the lipid compartments (intramyocellular [IMCL] and extramyocellular [EMCL] lipids) inside the musculature in these patients. The present study was designed to investigate the IMCL and EMCL, biochemical data, and functional performance in patients with severe OSA, and to examine the correlations between intramuscular lipid contents and test variables. PARTICIPANTS AND METHODS: Twenty patients with severe OSA (apnea-hypopnea index [AHI]: ≥30/h; body mass index [BMI]: 26.05±2.92) and 20 age- and BMI-matched controls (AHI <5/h) were enrolled. Proton magnetic resonance spectroscopy was used to measure the IMCL and EMCL of the right vastus lateralis muscle. Biochemical data, including levels of fasting plasma glucose, insulin, lipid profiles, and high-sensitivity C-reactive protein (hsCRP), were measured. Insulin resistance index (IR) was calculated using the homeostasis model assessment method. Performance tests included a cardiopulmonary exercise test and knee extension strength and endurance measurements. RESULTS: Patients with severe OSA had significantly (P<0.05) lower values of IMCL (14.1±5.4 AU) and EMCL (10.3±5.8 AU) compared to the control group (25.2±17.6 AU and 14.3±11.1 AU, respectively). Patients with severe OSA had significantly higher hsCRP, IR, and dyslipidemia compared with controls (all P<0.05). Furthermore, IMCL was negatively correlated with AHI, cumulative time with nocturnal pulse oximetric saturation lower than 90% (TSpO2<90%) (ρ=-0.35, P<0.05), IR (ρ=-0.40, P<0.05), glucose (ρ=-0.33, P<0.05), and insulin (ρ=-0.36, P<0.05), and positively correlated with lowest oximetric saturation (ρ=0.33, P<0.01). CONCLUSION: Skeletal muscle dysfunction and metabolic abnormalities were observed in patients with OSA that did not have obesity. IMCL was positively correlated with aerobic capacity and muscular performance, but negatively correlated with AHI and IR. Large-scale clinical trials are required to explore the complicated mechanism among OSA, intramuscular metabolism, and insulin action. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00813852.

2.
Eur J Radiol ; 120: 108671, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31629121

ABSTRACT

PURPOSE: To correlate the clinical stage and prognosis of oesophageal squamous cell carcinoma (SCC) using the imaging biomarkers from integrated positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS: In total, 54 consecutive patients with oesophageal SCC who receive PET/MRI scan were recruited before treatment. The imaging biomarkers used were the mean and minimal apparent diffusion coefficients (ADCmean and ADCmin), standardized uptake value (SUV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of tumours. The correlation between each imaging biomarker and survival was investigated using the Cox proportional hazards model. RESULTS: ADCmean was negatively correlated with SUVmax (r = -0.414, P =  0.025). ADCmin was negatively correlated with SUVmax (r = -0.423, P =  0.001) and SUVpeak (r = -0.402, P =  0.003), and was significantly lower in M1 than in M0 tumours (829.6 vs. 1069.8, P = 0.005). MTV was significantly higher in T3 + (P <  0.001), N1 + (P = 0.014) and TNM stage III + (P <  0.001) tumours. TLG was significantly higher in T3 + (P <  0.001), N1 + (P <  0.001), M1 (P =  0.045) and TNM stage III + (P <  0.001) tumours. The MTV/ADCmin ratio exhibited the highest area under the receiver operating characteristic curve (AUROC) for predicting M1 and advanced TNM stage tumours. Multivariate analysis for progression-free survival (PFS) and overall survival (OS) showed that a larger MTV/ADCmin was associated with a shorter PFS and OS (P = 0.024 and 0.046, respectively). CONCLUSION: The imaging biomarkers in integrated PET/MRI may predict clinical stage and survival in patients with oesophageal SCC.


Subject(s)
Esophageal Neoplasms/diagnosis , Esophageal Squamous Cell Carcinoma/pathology , Fluorodeoxyglucose F18 , Radiopharmaceuticals , Adult , Aged , Aged, 80 and over , Diffusion Magnetic Resonance Imaging/methods , Female , Glycolysis/physiology , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Multimodal Imaging/methods , Neoplasm Staging , Positron Emission Tomography Computed Tomography/methods , Prognosis , Proportional Hazards Models , Prospective Studies , ROC Curve , Retrospective Studies , Tumor Burden
3.
Eur Radiol ; 28(11): 4860-4870, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29770848

ABSTRACT

OBJECTIVES: The aim of this study is to investigate the correlation of survival outcomes with imaging biomarkers from multiparametric magnetic resonance imaging (MRI) in patients with brain metastases from breast cancer (BMBC). METHODS: This study was approved by the institutional review board. Twenty-two patients with BMBC who underwent treatment involving bevacizumab on day 1, etoposide on days 2-4, and cisplatin on day 2 in 21-day cycles were prospectively enrolled for a phase II study. Three brain MRIs were performed: before the treatment, on day 1, and on day 21. Eight imaging biomarkers were derived from dynamic contrast-enhanced MRI (Peak, IAUC60, Ktrans, kep, ve), diffusion-weighted imaging [apparent diffusion coefficient (ADC)], and MR spectroscopy (choline/N-acetylaspartate and choline/creatine ratios). The relative changes (Δ) in these biomarkers were correlated with the central nervous system (CNS)-specific progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier and Cox proportional hazard models. RESULTS: There were no significant differences in the survival outcomes as per the changes in the biomarkers on day 1. On day 21, those with a low ΔKtrans (p = 0.024) or ΔADC (p = 0.053) reduction had shorter CNS-specific PFS; further, those with a low ΔPeak (p = 0.012) or ΔIAUC60 (p = 0.04) reduction had shorter OS compared with those with high reductions. In multivariate analyses, ΔKtrans and ΔPeak were independent prognostic factors for CNS-specific PFS and OS, respectively, after controlling for age, size, hormone receptors, and performance status. CONCLUSIONS: Multiparametric MRI may help predict the survival outcomes in patients with BMBC. KEY POINTS: • Decreased angiogenesis after chemotherapy on day 21 indicated good survival outcome. • ΔK trans was an independent prognostic factors for CNS-specific PFS. • ΔPeak was an independent prognostic factors for OS. • Multiparametric MRI helps clinicians to assess patients with BMBC. • High-risk patients may benefit from more intensive follow-up or treatment strategies.


Subject(s)
Biomarkers, Tumor/analysis , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/secondary , Breast Neoplasms/pathology , Magnetic Resonance Imaging/methods , Adult , Aged , Antineoplastic Agents/therapeutic use , Aspartic Acid/analogs & derivatives , Aspartic Acid/analysis , Brain Neoplasms/drug therapy , Brain Neoplasms/mortality , Choline/analysis , Creatinine/analysis , Female , Humans , Kaplan-Meier Estimate , Magnetic Resonance Spectroscopy , Middle Aged , Proportional Hazards Models , Prospective Studies
4.
BMC Cancer ; 16: 466, 2016 07 13.
Article in English | MEDLINE | ID: mdl-27412562

ABSTRACT

BACKGROUND: To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. METHODS: Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60 , and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2-4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE-MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration. RESULTS: Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were -12.8 and -24.7 % for Peak, -46.6 and -65.8 % for Slope, -27.9 and -55.5 % for iAUC 60 , and -46.6 and -63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration. CONCLUSION: Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01281696 , registered prospectively on December 24, 2010.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Brain Neoplasms/drug therapy , Breast Neoplasms/pathology , Adult , Aged , Angiogenesis Inhibitors/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab/administration & dosage , Brain Neoplasms/blood supply , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/secondary , Breast Neoplasms/drug therapy , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Contrast Media/administration & dosage , Drug Administration Schedule , Drug Resistance, Neoplasm , Etoposide/administration & dosage , Etoposide/therapeutic use , Female , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Pilot Projects , Prospective Studies , Time Factors , Treatment Outcome
5.
Int J Nanomedicine ; 11: 2021-37, 2016.
Article in English | MEDLINE | ID: mdl-27274233

ABSTRACT

In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3O4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity (r 2) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity (r 1) (r 2/r 1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T2-weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy.


Subject(s)
Doxorubicin/therapeutic use , Drug Delivery Systems/methods , Magnetic Resonance Imaging/methods , Magnetics/methods , Magnetite Nanoparticles/chemistry , Neoplasms/drug therapy , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Proliferation/drug effects , Doxorubicin/pharmacology , Endocytosis/drug effects , HT29 Cells , Humans , Iron/metabolism , Male , Mice, Inbred BALB C , Mice, Nude , Neoplasms/pathology , Particle Size , Polyethylene Glycols/chemical synthesis , Polyethylene Glycols/chemistry , Proton Magnetic Resonance Spectroscopy , Rats, Sprague-Dawley , Silanes/chemical synthesis , Silanes/chemistry , Spectroscopy, Fourier Transform Infrared , Temperature , X-Ray Diffraction
6.
J Magn Reson Imaging ; 42(6): 1723-32, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25919115

ABSTRACT

PURPOSE: To evaluate the correlation between maximum standardized uptake value (SUVmax ) and minimum apparent diffusion coefficient (ADCmin ) of endometrial cancer derived from an integrated positron emission tomography / magnetic resonance (PET/MR) system and to determine their correlation with pathological prognostic factors. MATERIALS AND METHODS: This prospective study was approved by the Institutional Review Board of the hospital, and informed consent was obtained. Between April and December 2014, 47 consecutive patients with endometrial cancer were enrolled and underwent simultaneous PET/MR examinations before surgery. Thirty-six patients with measurable tumors on PET/MR were included for image analysis. Pearson's correlation coefficient was used to evaluate the correlation between SUVmax and ADCmin of the tumors. The Mann-Whitney U-test was utilized to evaluate relationships between these two imaging biomarkers and pathological prognostic factors. RESULTS: The mean SUVmax and ADCmin were 14.7 ± 7.1 and 0.48 ± 0.13 × 10(-3) mm(2) /s, respectively. A significant inverse correlation was found between SUVmax and ADCmin (r = -0.53; P = 0.001). SUVmax was significantly higher in tumors with advanced stage, deep myometrial invasion, cervical invasion, lymphovascular space involvement, and lymph node metastasis (P < 0.05). ADCmin was lower in tumors with higher grade, advanced stage, and cervical invasion (P < 0.05). The ratio of SUVmax to ADCmin was higher in tumors with higher grade, advanced stage, deep myometrial invasion, cervical invasion, lymphovascular space involvement, and lymph node metastasis (P < 0.05). CONCLUSION: SUVmax and ADCmin of endometrial cancer derived from integrated PET/MR are inversely correlated and are associated with pathological prognostic factors.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/epidemiology , Multimodal Imaging/methods , Positron-Emission Tomography/methods , Whole Body Imaging/methods , Adult , Aged , Aged, 80 and over , Computer Simulation , Female , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Metabolic Clearance Rate , Middle Aged , Models, Biological , Prevalence , Prognosis , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , Statistics as Topic , Systems Integration
7.
Clin Imaging ; 38(3): 287-91, 2014.
Article in English | MEDLINE | ID: mdl-24556332

ABSTRACT

OBJECTIVE: The objective was to compare vascular and hepatic enhancement differences at magnetic resonance imaging (MRI) between Gd-EOB-DTPA and Gd-DTPA in the same subjects. METHODS: Ten healthy subjects received dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA and then Gd-DTPA to obtain quantitative parameters at 60 and 100 s, respectively. RESULTS: At 60 s, no difference was noted in DCE-MRI parameters between the two contrast agents. At 100 s, mean transit time (MTT) was higher in Gd-EOB-DTPA than in Gd-DTPA (P=.008). CONCLUSIONS: Gd-EOB-DTPA showed vascular and hepatic enhancement similar to Gd-DTPA within the initial 60 s during the dynamic phase, but showed increased MTT due to hepatocytes uptake at 100 s.


Subject(s)
Contrast Media , Gadolinium DTPA , Image Enhancement/methods , Liver/blood supply , Liver/cytology , Magnetic Resonance Imaging/methods , Adult , Female , Hepatic Artery , Hepatic Veins , Humans , Magnetic Resonance Angiography , Male , Middle Aged , Portal Vein
8.
Invest Radiol ; 47(11): 649-55, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23011189

ABSTRACT

PURPOSE: The aim of this study was to evaluate the serial signal changes in hepatobiliary enhancement on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid or gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging and its correlation with clinical parameters. METHOD: Under institutional review board approval, Gd-EOB-DTPA-enhanced magnetic resonance imaging was performed in 77 subjects (21 healthy volunteers and 56 biopsy-proven chronic hepatitis patients), and the signal intensities of the liver and common hepatic ducts (CHD) were measured every 2 minutes up to 50 minutes postcontrast. The associations among hepatic and CHD signals, physiological and hematological variables, histological activity index, and Metavir scores were analyzed with Pearson correlation and multiple linear stepwise regressions. The predictive ability of contrast enhancement index (CEI) of the liver with histological activity index and fibrosis scores at different time points were studied using nonparametric receiver operating characteristic curves. RESULTS: Among the clinical parameters, body weight and body mass index had the highest negative correlation with hepatobiliary enhancement between 2 and 50 minutes postcontrast (P < 0.001). Multiple regressions showed that creatinine level, body weight, and body mass index were independent predictors for both mean hepatic and CHD signal intensity (P < 0.05). Patients with more severe fibrosis or moderate necrosis tended to have lower CEIs than other patients were. The predictive ability of CEI for the best differentiation between no fibrosis and any fibrosis (F ≥ 1) was at 10 minutes postcontrast (area under the receiver operating characteristic curve, 0.797). CONCLUSIONS: Delayed hepatobiliary enhancement with Gd-EOB-DTPA could be possibly used for staging liver fibrosis. Contrast enhancement index of the liver at 10 minutes is useful for differentiating between no fibrosis and any degree of fibrosis in chronic hepatitis patients.


Subject(s)
Common Bile Duct/pathology , Contrast Media , Gadolinium DTPA , Liver Cirrhosis/diagnosis , Liver Cirrhosis/pathology , Liver/pathology , Magnetic Resonance Imaging/methods , Adult , Body Mass Index , Female , Humans , Male , Predictive Value of Tests , Prospective Studies , Radiographic Image Enhancement/methods , Statistics as Topic , Time Factors
10.
Eur Radiol ; 22(1): 171-80, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21879400

ABSTRACT

OBJECTIVES: To develop a non-invasive MRI method for evaluation of liver fibrosis, with histological analysis as the reference standard. METHODS: The study protocol was approved by the Institutional Review Board for Human Studies of our hospital, and written informed consent was obtained from all subjects. Seventy-nine subjects who received dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA were divided into three subgroups according to Metavir score: no fibrosis (n = 30), mild fibrosis (n = 34), and advanced fibrosis (n = 15). The DCE-MRI parameters were measured using two models: (1) dual-input single-compartment model for arterial blood flow (F (a)), portal venous blood flow, total liver blood flow, arterial fraction (ART), distribution volume, and mean transit time; and (2) curve analysis model for Peak, Slope, and AUC. Statistical analysis was performed with Student's t-test and the nonparametric Kruskal-Wallis test. RESULTS: Slope and AUC were two best perfusion parameters to predict the severity of liver fibrosis (>F2 vs. ≦F2). Four significantly different variables were found between non-fibrotic versus mild-fibrotic subgroups: F (a), ART, Slope, and AUC; the best predictor for mild fibrosis was F (a) (AUROC:0.701). CONCLUSIONS: DCE-MRI with Gd-EOB-DTPA is a noninvasive imaging, by which multiple perfusion parameters can be measured to evaluate the severity of liver fibrosis.


Subject(s)
Contrast Media , Gadolinium DTPA , Hepatitis, Chronic/diagnosis , Liver Cirrhosis/diagnosis , Liver/blood supply , Magnetic Resonance Imaging , Adult , Algorithms , Area Under Curve , Blood Flow Velocity , Female , Hepatitis, Chronic/complications , Hepatitis, Chronic/physiopathology , Humans , Liver/pathology , Liver Cirrhosis/etiology , Liver Cirrhosis/physiopathology , Liver Function Tests , Magnetic Resonance Imaging/methods , Male , Prospective Studies , ROC Curve , Sensitivity and Specificity , Severity of Illness Index
11.
J Hepatol ; 55(4): 858-65, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21338641

ABSTRACT

BACKGROUND & AIMS: Sorafenib plus metronomic tegafur/uracil therapy can induce tumor stabilization in advanced hepatocellular carcinoma (HCC) patients. This study evaluated the correlation of vascular response measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and the clinical outcome. METHODS: DCE-MRI was performed in advanced HCC patients treated with sorafenib (800 mg/d) plus tegafur/uracil (250 mg/m(2)/d based on tegafur) at baseline and after 14 days of treatment. An operator-defined region of interest was placed in the most strongly enhanced area of the tumor to measure the pharmacokinetic parameter K(trans). Changes in K(trans) after treatment were correlated with the best tumor response and survival. RESULTS: Thirty-one patients were evaluable. There were one partial response (PR), 18 stable disease (SD), and 12 progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Baseline K(trans) was higher in patients with PR or SD (median 1215.2 × 10(-3)/min, range 582.5-4555.3 × 10(-3)/min) than patients with PD (median 702.0 × 10(-3)/min, range 375.2-1938.0 × 10(-3)/min, p = 0.008). After 14 days of study treatment, the median K(trans) change was -47.1% (range -87.0 to -18.0%) in patients with PR or SD, and 9.6% (range -44.8 to +81%) in those with PD (p<0.001). A vascular response, defined by a 40% or greater decrease in K(trans) after 14 days of study treatment, correlated with longer progression-free survival (median 29.1 vs. 8.7 weeks, p = 0.033) and overall survival (median 53.0 vs. 14.9 weeks, p = 0.016). Percentage of K(trans) change after treatment is an independent predictor of tumor response, progression-free survival, and overall survival. CONCLUSIONS: K(trans) measured by DCE-MRI correlated well with tumor response and survival in HCC patients who received sorafenib plus metronomic tegafur/uracil therapy.


Subject(s)
Benzenesulfonates/administration & dosage , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Magnetic Resonance Imaging/methods , Pyridines/administration & dosage , Tegafur/administration & dosage , Uracil/administration & dosage , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Contrast Media , Feasibility Studies , Female , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/mortality , Neovascularization, Pathologic/pathology , Niacinamide/analogs & derivatives , Phenylurea Compounds , Predictive Value of Tests , Sorafenib , Young Adult
12.
Radiology ; 258(3): 821-31, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21212370

ABSTRACT

PURPOSE: To examine whether dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging measurement of bone marrow perfusion in acute myeloid leukemia (AML) patients in complete remission (CR) is associated with outcome and survival. MATERIALS AND METHODS: After institutional review board approval and informed consent were obtained, from September 2004 to October 2007, 51 patients (29 women, 22 men; mean age, 43.5 years; range, 17-66 years) agreed to undergo DCE MR imaging to assess bone marrow perfusion, among 96 patients with newly diagnosed de novo AML who had received induction chemotherapy and achieved CR. Two semiquantitative parameters (peak and slope) and another three quantitative parameters (amplitude, K(ep) [efflux rate constant], and K(el) [elimination rate constant]) were calculated. Overall survival (OS) and relapse-free survival (RFS) were assessed with the Kaplan-Meier model, while differences between patient groups with high and low DCE MR imaging parameter values were assessed by using the two-sided log-rank test. RESULTS: The median follow-up was 25.9 months. Univariate analysis results showed that high values of peak (≥0.42), slope (≥0.0235), amplitude (≥0.03), and K(ep) (≥0.0082) were associated with shorter OS (P = .004, 0.01, 0.034, and 0.026, respectively). Besides, a high value of K(ep) was also associated with shorter RFS (P = .008). When age, sex, and initial karyotype at diagnosis were included in multivariate Cox proportional hazards analysis, the results showed that only K(ep), but not other DCE MR imaging parameters, was an independent factor for OS (relative risk [RR], 30.305; P = .021) and RFS (RR, 6.477; P = .009). CONCLUSION: Bone marrow perfusion measured with DCE MR imaging in AML patients in CR can be an indicator of outcome and survival. K(ep) measured with kinetic modeling was useful and significantly associated with RFS, while heuristic parameters (peak and slope) were not.


Subject(s)
Bone Marrow/pathology , Leukemia, Myeloid, Acute/pathology , Magnetic Resonance Imaging/methods , Adolescent , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Contrast Media , Female , Gadolinium DTPA , Humans , Leukemia, Myeloid, Acute/drug therapy , Male , Middle Aged , Proportional Hazards Models , Remission Induction , Survival Rate , Treatment Outcome
13.
Radiology ; 252(3): 704-11, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19717751

ABSTRACT

PURPOSE: To evaluate pancreatic perfusion by using dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with pharmacokinetic modeling in coronary artery disease (CAD) patients with and those without type 2 diabetes to determine which perfusion parameter alterations might be associated with type 2 diabetes. MATERIALS AND METHODS: This prospective study was approved by the responsible institutional review board. Written informed consent was obtained from all patients. All patients studied had CAD documented at conventional angiography. DCE MR with a two-dimensional T1-weighted fast low-angle shot sequence in oblique axial planes was used to assess pancreatic microcirculation in patients with and those without type 2 diabetes (age +/- standard deviation, 60.8 years +/- 11.2 and 61.8 years +/- 11.2, respectively; 20 men and five women in each group). Microcirculatory quantitative parameters, including volume transfer constant (K(trans), in min(-1)), extravascular extracellular space volume per unit volume of tissue (v(e)), and plasma volume per unit volume of tissue (v(p)) were compared between groups by using independent-sample t tests. RESULTS: Patients with diabetes had a significantly higher K(trans) (0.977 vs 0.696, P = .031) and a lower v(p) (0.057 vs 0.084, P = .005) compared with patients without diabetes. A borderline difference in v(e) was found between the diabetes and nondiabetes groups (0.141 vs 0.103, P = .05). Among the 25 patients with diabetes, those who had the condition for more than 10 years (n = 11) had significantly higher K(trans) and v(e) than did those who had diabetes for less than 10 years (n = 14) (1.145 vs 0.783 and 0.174 vs 0.108; P = .04 and .02, respectively). CONCLUSION: DCE MR imaging demonstrated increased endothelial permeability and decreased plasma volume in the pancreas in CAD patients with type 2 diabetes; patients with a history of diabetes for more than 10 years showed further increase in endothelial permeability.


Subject(s)
Coronary Artery Disease/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Magnetic Resonance Imaging/methods , Pancreas/blood supply , Aged , Aged, 80 and over , Contrast Media/pharmacokinetics , Coronary Artery Disease/complications , Diabetes Mellitus, Type 2/complications , Female , Humans , Male , Microcirculation , Middle Aged , Prospective Studies , Reproducibility of Results
14.
Blood ; 113(14): 3161-7, 2009 Apr 02.
Article in English | MEDLINE | ID: mdl-18988863

ABSTRACT

Emerging evidence suggests that progression of hematologic malignancies is associated with angiogenesis. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can provide global and functional imaging of tumor angiogenesis. In this study, we performed bone marrow DCE-MRI prospectively at diagnosis and after induction chemotherapy in 78 de novo acute myeloid leukemia (AML) patients and correlated it with treatment outcome. An algorithm to assess bone marrow angiogenesis by measuring the DCE-MRI time-intensity curve pixel by pixel was developed using 3 distinct parameters: peak enhancement ratio (Peak) to indicate tissue blood perfusion; amplitude (Amp) to reflect vascularity; and volume transfer constant (K trans) to indicate vascular permeability. The Peak and Amp decreased significantly at remission status after induction chemotherapy. Patients with higher Peak or Amp at diagnosis had shorter overall survival and disease-free survival than others. Cox multivariate analysis identified higher Peak value (hazard ratio, 9.181; 95% confidence interval, 1.740-48.437; P = .009) as an independent predictor for overall survival in addition to unfavorable karyotype and old age. Our findings provide evidence that increased bone marrow angiogenesis measured by DCE-MRI can predict adverse clinical outcome in AML patients. DCE-MRI may help to select high-risk phenotype AML patients for tailored antiangiogenic therapy and to monitor treatment response.


Subject(s)
Bone Marrow/blood supply , Leukemia, Myeloid, Acute/diagnostic imaging , Leukemia, Myeloid, Acute/mortality , Neovascularization, Pathologic/diagnostic imaging , Adolescent , Adult , Aged , Bone Marrow/diagnostic imaging , Female , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/therapy , Magnetic Resonance Imaging/methods , Male , Middle Aged , Prognosis , Radiography , Survival Analysis , Up-Regulation/physiology , Young Adult
15.
Spine (Phila Pa 1976) ; 29(24): 2844-50, 2004 Dec 15.
Article in English | MEDLINE | ID: mdl-15599288

ABSTRACT

STUDY DESIGN: Prospective study. OBJECTIVES: To assess the proton MR spectroscopy (1H MRS) of vertebral bone marrow and correlate the lipid water ratio (LWR) and spectral line width (LW) with bone mineral density (BMD) in female subjects. SUMMARY OF BACKGROUND DATA: The mechanism of bone marrow fat accumulation and bone mineral content is poorly understood. Proton MR spectroscopy was used to demonstrate the lipid and water spectra in the bone marrow. We try to assess the possible interaction between the bone marrow lipid content, aging, and BMD. METHODS: Proton MRS and BMD of the lumbar spine were performed in 52 female subjects (mean age, 58 years; SD, 10 years). They were 13 premenopausal and 39 postmenopausal women. The BMD (g/cm2) was measured using dual energy radiograph absorptiometry at the lumbar spine. Single voxel 1H MRS was measured at L3 vertebral body by stimulated echo-acquisition mode (STEAM) sequence and demonstrated two major peaks (lipid and water). Comparisons of the differences between the two subgroups were made. Pearson's correlation was also calculated to explore the association of 1H MRS measurements with age and BMD. Partial correlation was further conducted when controlling the variable such as age or BMD. RESULTS: BMD and LWR had statistically significant difference between the pre- and postmenopausal subgroups (P < 0.001), while lipid LW had a borderline difference and water LW had no difference. LWR was positively correlated with age (r = 0.52 and P < 0.0001) and negatively correlated with BMD (r = -0.40 and P = 0.003) for all the subjects. Lipid LW was negatively correlated with age (r = -0.32 and P = 0.0197) and positively correlated with BMD (r = 0.67 and P < 0.0001). When controlling for BMD effect, only LWR is statistically correlated with age (partial r = 0.39, P = 0.0045), while only the lipid LW is statistically correlated with BMD when controlling for age (partial r = 0.63, P < 0.0001). None of the correlations between water LW and age or BMD was significant. In the subgroups, only the lipid LW is significantly correlated with BMD (r = 0.78, P = 0.0016 in premenopausal women; r = 0.62, P < 0.0001 in postmenopausal women). CONCLUSION: The LWR had a positive correlation with the age, while the lipid LW had a positive correlation with BMD, even after controlling the age factor. The bone marrow lipid water content and metabolism acted as important roles in the internal environment of bone and influenced bone mineralization.


Subject(s)
Bone Density , Bone Marrow/chemistry , Lipids/analysis , Lumbar Vertebrae/metabolism , Water/analysis , Absorptiometry, Photon , Adult , Aged , Bone Marrow/metabolism , Female , Humans , Lipid Metabolism , Magnetic Resonance Spectroscopy , Middle Aged , Postmenopause , Premenopause , Water/metabolism
16.
Radiology ; 233(1): 121-8, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15317948

ABSTRACT

PURPOSE: To prospectively assess lumbar spine bone marrow perfusion at dynamic magnetic resonance (MR) imaging and correlate perfusion with bone mineral density (BMD) in female subjects. MATERIALS AND METHODS: BMD measurement and dynamic MR imaging of the lumbar spine were performed in 69 female subjects (mean age +/- standard deviation, 57 years +/- 11). Subjects were stratified into premenopausal (n = 19) and postmenopausal (n = 50) groups, with the latter group including both women who were (n = 13) and women who were not (n = 37) receiving hormone replacement therapy. BMD (in grams per square centimeter) was measured with dual energy absorptiometry in the lumbar spine. Peak enhancement ratio, measured with time-signal intensity curves calculated from dynamic MR image data, represented bone marrow perfusion. Peak enhancement ratio was compared with age and BMD by using linear regression analysis and Pearson correlation. RESULTS: A significant positive correlation was found for BMD with peak enhancement ratio of lumbar vertebrae among all subjects (n = 69, r = 0.63, P <.001), all postmenopausal women (n = 50, r = 0.50, P <.001), and postmenopausal women without hormone replacement therapy (n = 37, r = 0.61, P <.001). However, the correlation between BMD and peak enhancement ratio was not significant (P >.05) in premenopausal women (n = 19) or postmenopausal women receiving hormone therapy (n = 13). Both BMD and peak enhancement ratio were inversely correlated with age (P <.001, Pearson correlation). Pearson partial correlation coefficient for peak enhancement ratio and mean in all subjects, with control for inverse correlation with age, was significant (r = 0.63, P <.001). CONCLUSION: Significant correlation was found between the peak enhancement ratio of vertebral bone marrow and BMD in postmenopausal female subjects. This result may suggest a vascular component in the pathogenesis of osteoporosis.


Subject(s)
Bone Density , Bone Marrow/blood supply , Lumbar Vertebrae/blood supply , Magnetic Resonance Imaging , Absorptiometry, Photon , Adult , Age Factors , Aged , Bone Density/physiology , Contrast Media , Female , Hormone Replacement Therapy , Humans , Image Enhancement , Linear Models , Middle Aged , Postmenopause/physiology , Premenopause/physiology , Prospective Studies , Regional Blood Flow/physiology
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