Repeatability and reproducibility of cardiac manganese-enhanced magnetic resonance imaging.

Manganese-enhanced magnetic resonance imaging can provide a surrogate measure of myocardial calcium handling. Its repeatability and reproducibility are currently unknown. Sixty-eight participants: 20 healthy volunteers, 20 with acute myocardial infarction, 18 with hypertrophic and 10 with non-ischemic dilated cardiomyopathy underwent manganese-enhanced magnetic resonance imaging. Ten healthy volunteers were re-scanned at 3 months. Native T1 values and myocardial manganese uptake were assessed for intra and inter-observer repeatability. Scan-rescan reproducibility was assessed in ten healthy volunteers. Intra-observer and inter-observer correlation was excellent in healthy volunteers for mean native T1 mapping [Lin's correlation coefficient (LCC) 0.97 and 0.97 respectively] and myocardial manganese uptake (LCC: 0.99 and 0.96 respectively). Scan-rescan correlation for native T1 and myocardial manganese uptake was also excellent. Similarly, intra-observer correlations for native T1 and myocardial manganese uptake in patients with acute myocardial infarction (LCC: 0.97 and 0.97 respectively), hypertrophic (LCC: 0.98 and 0.97 respectively) and dilated cardiomyopathy (LCC: 0.99 and 0.95 respectively) were excellent. Limits of agreement were broader in patients with dilated cardiomyopathy. Manganese-enhanced magnetic resonance imaging has high repeatability and reproducibility in healthy myocardium and high repeatability in diseased myocardium. However, further study is needed to establish robustness in pathologies with diffuse myocardial fibrosis.

Manganese-enhanced magnetic resonance imaging in dilated cardiomyopathy and hypertrophic cardiomyopathy.

AIMS: The aim of this study is to quantify altered myocardial calcium handling in non-ischaemic cardiomyopathy using magnetic resonance imaging. METHODS AND RESULTS: Patients with dilated cardiomyopathy (n = 10) or hypertrophic cardiomyopathy (n = 17) underwent both gadolinium and manganese contrast-enhanced magnetic resonance imaging and were compared with healthy volunteers (n = 20). Differential manganese uptake (Ki) was assessed using a two-compartment Patlak model. Compared with healthy volunteers, reduction in T1 with manganese-enhanced magnetic resonance imaging was lower in patients with dilated cardiomyopathy [mean reduction 257 ± 45 (21%) vs. 288 ± 34 (26%) ms, P < 0.001], with higher T1 at 40 min (948 ± 57 vs. 834 ± 28 ms, P < 0.0001). In patients with hypertrophic cardiomyopathy, reductions in T1 were less than healthy volunteers [mean reduction 251 ± 86 (18%) and 277 ± 34 (23%) vs. 288 ± 34 (26%) ms, with and without fibrosis respectively, P < 0.001]. Myocardial manganese uptake was modelled, rate of uptake was reduced in both dilated and hypertrophic cardiomyopathy in comparison with healthy volunteers (mean Ki 19 ± 4, 19 ± 3, and 23 ± 4 mL/100 g/min, respectively; P = 0.0068). In patients with dilated cardiomyopathy, manganese uptake rate correlated with left ventricular ejection fraction (r2 = 0.61, P = 0.009). Rate of myocardial manganese uptake demonstrated stepwise reductions across healthy myocardium, hypertrophic cardiomyopathy without fibrosis and hypertrophic cardiomyopathy with fibrosis providing absolute discrimination between the healthy myocardium and fibrosed myocardium (mean Ki 23 ± 4, 19 ± 3, and 13 ± 4 mL/100 g/min, respectively; P < 0.0001). CONCLUSION: The rate of manganese uptake in both dilated and hypertrophic cardiomyopathy provides a measure of altered myocardial calcium handling. This holds major promise for the detection and monitoring of dysfunctional myocardium, with the potential for early intervention and prognostication.

Manganese-Enhanced T1 Mapping in the Myocardium of Normal and Infarcted Hearts.

Background: Manganese-enhanced MRI (MEMRI) has the potential to identify viable myocardium and quantify calcium influx and handling. Two distinct manganese contrast media have been developed for clinical application, mangafodipir and EVP1001-1, employing different strategies to mitigate against adverse effects resulting from calcium-channel agonism. Mangafodipir delivers manganese ions as a chelate, and EVP1001-1 coadministers calcium gluconate. Using myocardial T1 mapping, we aimed to explore chelated and nonchelated manganese contrast agents, their mechanism of myocardial uptake, and their application to infarcted hearts. Methods: T1 mapping was performed in healthy adult male Sprague-Dawley rats using a 7T MRI scanner before and after nonchelated (EVP1001-1 or MnCl2 (22 µmol/kg)) or chelated (mangafodipir (22-44 µmol/kg)) manganese-based contrast media in the presence of calcium channel blockade (diltiazem (100-200 µmol/kg/min)) or sodium chloride (0.9%). A second cohort of rats underwent surgery to induce anterior myocardial infarction by permanent coronary artery ligation or sham surgery. Infarcted rats were imaged with standard gadolinium delayed enhancement MRI (DEMRI) with inversion recovery techniques (DEMRI inversion recovery) as well as DEMRI T1 mapping. A subsequent MEMRI scan was performed 48 h later using either nonchelated or chelated manganese and T1 mapping. Finally, animals were culled at 12 weeks, and infarct size was quantified histologically with Masson's trichrome (MTC). Results: Both manganese agents induced concentration-dependent shortening of myocardial T1 values. This was greatest with nonchelated manganese, and could be inhibited by 30-43% with calcium-channel blockade. Manganese imaging successfully delineated the area of myocardial infarction. Indeed, irrespective of the manganese agent, there was good agreement between infarct size on MEMRI T1 mapping and histology (bias 1.4%, 95% CI -14.8 to 17.1 P>0.05). In contrast, DEMRI inversion recovery overestimated infarct size (bias 11.4%, 95% CI -9.1 to 31.8 P=0.002), as did DEMRI T1 mapping (bias 8.2%, 95% CI -10.7 to 27.2 P=0.008). Increased manganese uptake was also observed in the remote myocardium, with remote myocardial ∆T1 inversely correlating with left ventricular ejection fraction after myocardial infarction (r=-0.61, P=0.022). Conclusions: MEMRI causes concentration and calcium channel-dependent myocardial T1 shortening. MEMRI with T1 mapping provides an accurate assessment of infarct size and can also identify changes in calcium handling in the remote myocardium. This technique has potential applications for the assessment of myocardial viability, remodelling, and regeneration.

Multimodality quantitative assessments of myocardial perfusion using dynamic contrast enhanced magnetic resonance and 15O-labelled water positron emission tomography imaging.

Kinetic modelling of myocardial perfusion imaging data allows the absolute quantification of myocardial blood flow (MBF) and can improve the diagnosis and clinical assessment of coronary artery disease (CAD). Positron emission tomography (PET) imaging is considered the reference standard technique for absolute quantification, whilst oxygen-15 (15O)-water has been extensively implemented for MBF quantification. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has also been used for MBF quantification and showed comparable diagnostic performance against (15O)-water PET studies. We investigated for the first time the diagnostic performance of two different PET MBF analysis softwares PMOD and Carimas, for obstructive CAD detection against invasive clinical standard methods in 20 patients with known or suspected CAD. Fermi and distributed parameter modelling-derived MBF quantification from DCE-MRI was also compared against (15O)-water PET, in a subgroup of 6 patients. The sensitivity and specificity for PMOD was significantly superior for obstructive CAD detection in both per vessel (0.83, 0.90) and per patient (0.86, 0.75) analysis, against Carimas (0.75, 0.65), (0.81, 0.70), respectively. We showed strong, significant correlations between MR and PET MBF quantifications (r=0.83-0.92). However, DP and PMOD analysis demonstrated comparable and higher haemodynamic differences between obstructive versus (no, minor or non)-obstructive CAD, against Fermi and Carimas analysis. Our MR method assessments against the optimum PET reference standard technique for perfusion analysis showed promising results in per segment level and can support further multi-modality assessments in larger patient cohorts. Further MR against PET assessments may help to determine their comparative diagnostic performance for obstructive CAD detection.

Utility and cost evaluation of multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease.

BACKGROUND: Validated diagnostic tools that are accurate, cost effective and acceptable to patients are required for disease stratification and monitoring in NAFLD. AIMS: To investigate the performance and cost of multiparametric MRI alongside existing biomarkers in the assessment of NAFLD. METHODS: Adult patients undergoing standard of care liver biopsy for NAFLD were prospectively recruited at two UK liver centres and underwent multiparametric MRI, blood sampling and transient elastography withing 2 weeks of liver biopsy. Non-invasive markers were compared to histology as the gold standard. RESULTS: Data were obtained in 50 patients and 6 healthy volunteers. Corrected T1 (cT1) correlated with NAFLD activity score (ρ = 0.514, P < .001). cT1, enhanced liver fibrosis (ELF) test and liver stiffness differentiated patients with simple steatosis and NASH with AUROC (95% CI) of 0.69 (0.50-0.88), 0.87 (0.77-0.79) and 0.82 (0.70-0.94) respectively and healthy volunteers from patients with AUROC (95% CI) of 0.93 (0.86-1.00), 0.81 (0.69-0.92) and 0.89 (0.77-1.00) respectively. For the risk stratification of NAFLD, multiparametric MRI could save £150,218 per 1000 patients compared to biopsy. Multiparametric MRI did not discriminate between individual histological fibrosis stages in this population (P = .068). CONCLUSIONS: Multiparametric MRI accurately identified patients with steatosis, stratifies those with NASH or simple steatosis and reliably excludes clinically significant liver disease with superior negative predictive value (83.3%) to liver stiffness (42.9%) and ELF (57.1%). For the risk stratification of NAFLD, multiparametric MRI was cost effective and, combined with transient elastography, had the lowest cost per correct diagnosis.

Brain Development in Fetuses of Mothers with Diabetes: A Case-Control MR Imaging Study.

BACKGROUND AND PURPOSE: Offspring exposed to maternal diabetes are at increased risk of neurocognitive impairment, but its origins are unknown. With MR imaging, we investigated the feasibility of comprehensive assessment of brain metabolism (1H-MRS), microstructure (DWI), and macrostructure (structural MRI) in third-trimester fetuses in women with diabetes and determined normal ranges for the MR imaging parameters measured. MATERIALS AND METHODS: Women with singleton pregnancies with diabetes (n = 26) and healthy controls (n = 26) were recruited prospectively for MR imaging studies between 34 and 38 weeks' gestation. RESULTS: Data suitable for postprocessing were obtained from 79%, 71%, and 46% of women for 1H-MRS, DWI, and structural MRI, respectively. There was no difference in the NAA/Cho and NAA/Cr ratios (mean [SD]) in the fetal brain in women with diabetes compared with controls (1.74 [0.79] versus 1.79 [0.64], P = .81; and 0.78 [0.28] versus 0.94 [0.36], P = .12, respectively), but the Cho/Cr ratio was marginally lower (0.46 [0.11] versus 0.53 [0.10], P = .04). There was no difference in mean [SD] anterior white, posterior white, and deep gray matter ADC between patients and controls (1.16 [0.12] versus 1.16 [0.08], P = .96; 1.54 [0.16] versus 1.59 [0.20], P = .56; and 1.49 [0.23] versus 1.52 [0.23], P = .89, respectively) or volume of the cerebrum (243.0 mL [22.7 mL] versus 253.8 mL [31.6 mL], P = .38). CONCLUSIONS: Acquiring multimodal MR imaging of the fetal brain at 3T from pregnant women with diabetes is feasible. Further study of fetal brain metabolism in maternal diabetes is warranted.

Assessment of myocardial fibrosis with T1 mapping MRI.

Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson-Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present.

Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms.

OBJECTIVES: Inflammation is critical in the pathogenesis of abdominal aortic aneurysm (AAA) disease. Combined (18)F-fludeoxyglucose ((18)F-FDG) positron emission tomography with computed tomography (PET-CT) and ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) are non-invasive methods of assessing tissue inflammation. The aim of this study was to compare these techniques in patients with AAA. MATERIALS AND METHODS: Fifteen patients with asymptomatic AAA with diameter 46 ± 7 mm underwent PET-CT with (18)F-FDG, and T2*-weighted MRI before and 24 hours after administration of USPIO. The PET-CT and MRI data were then co-registered. Standardised uptake values (SUVs) were calculated to measure (18)F-FDG activity, and USPIO uptake was determined using the change in R2*. Comparisons between the techniques were made using a quadrant analysis and a voxel-by-voxel evaluation. RESULTS: When all areas of the aneurysm were evaluated, there was a modest correlation between the SUV on PET-CT and the change in R2* on USPIO-enhanced MRI (n = 70,345 voxels; r = .30; p < .0001). Although regions of increased (18)F-FDG and USPIO uptake co-localised on occasion, this was infrequent (kappa statistic 0.074; 95% CI 0.026-0.122). (18)F-FDG activity was commonly focused in the shoulder region whereas USPIO uptake was more apparent in the main body of the aneurysm. Maximum SUV was lower in patients with mural USPIO uptake. CONCLUSIONS: Both (18)F-FDG PET-CT and USPIO-MRI uptake identify vascular inflammation associated with AAA. Although they demonstrate a modest correlation, there are distinct differences in the pattern and distribution of uptake, suggesting a differential detection of macrophage glycolytic and phagocytic activity respectively.

Epigenomic profiling of preterm infants reveals DNA methylation differences at sites associated with neural function.

DNA methylation (DNAm) plays a determining role in neural cell fate and provides a molecular link between early-life stress and neuropsychiatric disease. Preterm birth is a profound environmental stressor that is closely associated with alterations in connectivity of neural systems and long-term neuropsychiatric impairment. The aims of this study were to examine the relationship between preterm birth and DNAm, and to investigate factors that contribute to variance in DNAm. DNA was collected from preterm infants (birth<33 weeks gestation) and healthy controls (birth>37 weeks), and a genome-wide analysis of DNAm was performed; diffusion magnetic resonance imaging (dMRI) data were acquired from the preterm group. The major fasciculi were segmented, and fractional anisotropy, mean diffusivity and tract shape were calculated. Principal components (PC) analysis was used to investigate the contribution of MRI features and clinical variables to variance in DNAm. Differential methylation was found within 25 gene bodies and 58 promoters of protein-coding genes in preterm infants compared with controls; 10 of these have neural functions. Differences detected in the array were validated with pyrosequencing. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 PCs; corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC. Preterm birth is associated with alterations in the methylome at sites that influence neural development and function. Differential methylation analysis has identified several promising candidate genes for understanding the genetic/epigenetic basis of preterm brain injury.

The biological correlates of macroscopic breast tumour structure measured using fractal analysis in patients undergoing neoadjuvant chemotherapy.

Breast cancers are evolving, multi-scale systems that are characterized by varied complex spatial structures. In this study, we measured the structural characteristics of 33 breast tumours in patients who were to receive neoadjuvant chemotherapy using dynamic contrast enhanced MRI and fractal geometry. The results showed a significant association between fractal measurements and tumour characteristics. The fractal dimension was associated with receptor status (ER and PR) and the fractal fit was associated with response to chemotherapy, measured using a validated pathological response scale, tumour grade and size. This study describes structure measures that may be a consequence of known prognostic factors during the initial and/or maturation phase of tumour growth. These results suggest that measuring tumour structure in this way can predict an individual's response to neoadjuvant therapy and may identify those who will benefit least from neoadjuvant chemotherapy, allowing alternative treatment options to be selected in those patients.

Use of a capillary input function with cardiac output for the estimation of lesion pharmacokinetic parameters: preliminary results on a breast cancer patient.

The objective of this work was to propose and demonstrate a novel technique for the assessment of tumour pharmacokinetic parameters together with a regionally estimated vascular input function. A breast cancer patient T2*-weighted dynamic contrast enhanced MRI (DCE-MRI) dataset acquired at high temporal resolution during the first-pass bolus perfusion was used for testing the technique. Extraction of the lesion volume transfer constant K(trans) together with the intravascular plasma volume fraction v(p) was achieved by optimizing a capillary input function with a measure of cardiac output using the principle of intravascular indicator dilution theory. For a region of interest drawn within the breast lesion a v(p) of 0.16 and a K(trans) of 0.70 min(-1) were estimated. Despite the value of v(p) being higher than expected, estimated K(trans) was in accordance with the literature values. In conclusion, the technique proposed here, has the main advantage of allowing the estimation of breast tumour pharmacokinetic parameters from first-pass perfusion T2*-weighted DCE-MRI data without the need of measuring an arterial input function. The technique may also have applicability to T1-weighted DCE-MRI data.

The accuracy of pharmacokinetic parameter measurement in DCE-MRI of the breast at 3 T.

The purpose of this work is to quantify the accuracy of pharmacokinetic parameter measurement in DCE-MRI of breast cancer at 3 T in relation to three sources of error. Individually, T1 measurement error, temporal resolution and transmitted RF field inhomogeneity are considered. Dynamic contrast enhancement curves were simulated using standard acquisition parameters of a DCE-MRI protocol. Errors on pre-contrast T1 due to incorrect RF spoiling were considered. Flip angle errors were measured and introduced into the fitting routine, and temporal resolution was also varied. The error in fitted pharmacokinetic parameters, K(trans) and v(e), was calculated. Flip angles were found to be reduced by up to 55% of the expected value. The resultant errors in our range of K(trans) and v(e) were found to be up to 66% and 74%, respectively. Incorrect T1 estimation results in K(trans) and v(e) errors up to 531% and 233%, respectively. When the temporal resolution is reduced from 10 to 70 s K(trans) drops by up to 48%, while v(e) shows negligible variation. In combination, uncertainties in tissue T1 map and applied flip angle were shown to contribute to errors of up to 88% in K(trans) and 73% in v(e). These results demonstrate the importance of high temporal resolution, accurate T1 measurement and good B1 homogeneity.

Depth-dependent swimbladder compression in herring Clupea harengus observed using magnetic resonance imaging.

Changes in swimbladder morphology in an Atlantic herring Clupea harengus with pressure were examined by magnetic resonance imaging of a dead fish in a purpose-built pressure chamber. Swimbladder volume changed with pressure according to Boyle's Law, but compression in the lateral aspect was greater than in the dorsal aspect. This uneven compression has a reduced effect on acoustic backscattering than symmetrical compression and would elicit less pronounced effects of depth on acoustic biomass estimates of C. harengus.

Blood oxygen level-dependent (BOLD) magnetic resonance imaging in patients with dypiridamole induced ischaemia; a PET comparative study.

BACKGROUND: Blood oxygen level-dependent (BOLD) MRI relies on changes in deoxyhaemoglobin level in tissues under stress for signal variation and may be used for detection of ischaemic myocardium. METHODS: 15 patients with stress induced myocardial ischaemia on PET scanning underwent rest and dypiridamole stress MRI using a double breath-hold T2-weighted, ECG gated sequence to produce BOLD contrast images and cine-MRI for wall thickening assessment. Signal change on BOLD MRI and wall thickening were compared between rest and stress images in ischaemic and non-ischaemic myocardial segments. RESULTS: Using PET, 156 segments were identified with reversible ischaemia and 324 as non-ischaemic. The ischaemic segments were found on BOLD MRI to have an average signal change between rest and stress of -16.7% compared to -14% in the non-ischaemic segments (p=0.04). The average wall thickening was 7.8 mm in the ischaemic segments compared with 9.5 mm in the non-ischaemic segments (p<0.0001). CONCLUSION: BOLD MRI with wall thickening assessment may differentiate ischaemic from non-ischaemic myocardium in patients with stress induced myocardial ischaemia. Larger studies with improved spatial resolution would help define a threshold for detection of ischaemia as well as determine this technique's sensitivity and specificity.

Blood oxygen level dependent (BOLD) MRI: A novel technique for the detection of myocardial ischemia.

BACKGROUND: Blood oxygen level dependent (BOLD) T2* MRI detects signal variance within the myocardium based on changes in the deoxyhaemoglobin level following pharmacological stress, and it has the potential to identify areas of myocardial ischemia. The aim of the present study was to assess the utility of BOLD T2* MRI in the detection of myocardial ischemia in patients with an existing diagnosis of coronary artery disease. METHOD: Twenty-one patients with established three-vessel coronary artery disease on coronary angiography underwent rest and dipyridamole stress MRI using a double breath-hold T2* weighted ECG gated sequence. Analysis was performed on multiple short-axis slices of the heart, projected as a bull's eye. The myocardium was divided into three coronary territories, yielding 63 territories in total. A signal change between rest and stress of more than +/-4% was significant, implying a change in deoxyhaemoglobin concentration. A signal decrease or no changes denote the presence of ischemia, while a signal increase indicates no ischemia. RESULTS: All images were of sufficient quality for signal intensity analysis. In 12/63 territories (19%), a significant signal increase following stress was detected. A significant signal decrease was detected in 34/63 territories (54%), and in 17/63 territories (27%) there was a non-significant change. The presence of a perfusion defect was identified, therefore, in 51/63 (81%), based on the signal difference between rest and stress. CONCLUSION: Changes in myocardial oxygen level appear to be detectable by BOLD T2* MRI without using contrast media. Further, larger comparative studies are required to evaluate the diagnostic and prognostic impact of this technique and to compare it to the gold standard methods for the detection of myocardial ischemia.

Baseline MRI delivery characteristics predict change in invasive ductal breast carcinoma PET metabolism as a result of primary chemotherapy administration.

BACKGROUND: The aim of the study was to investigate whether pre-therapy vascular delivery assessment [using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)] can predict reduction in breast cancer metabolism [detected using 2-[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography ((18)F(-)FDG-PET)] after a single cycle of chemotherapy. Reduction in (18)F-FDG PET metabolism has previously been shown to correlate with histological response to primary chemotherapy. PATIENTS AND METHODS: Seventeen patients with large or locally advanced invasive ductal carcinomas of the breast were imaged using DCE-MRI and (18)F-FDG-PET prior to therapy and 20 days after the first cycle of chemotherapy. MRI data were analysed using a multi-compartment model. PET data were analysed using standardised uptake value (SUV) analysis. RESULTS: A significant association (P <0.05) was observed between pre-therapy DCE-MRI vascular parameters and the reduction in PET metabolism resulting from administration of one cycle of chemotherapy. CONCLUSIONS: A relationship was demonstrated between pre-therapy DCE-MRI vascular parameters and the reduction in PET metabolism after a single cycle of chemotherapy. This suggests that reduction in PET metabolism as a result of chemotherapy may be dependent, at least in part, on pre-therapy vascular delivery. These pre-therapy vascular characteristics may be suitable for use as a surrogate measure for initial chemotherapy delivery, a key factor in chemotherapeutic efficacy.

The use of the Levenberg-Marquardt curve-fitting algorithm in pharmacokinetic modelling of DCE-MRI data.

The use of curve-fitting and compartmental modelling for calculating physiological parameters from measured data has increased in popularity in recent years. Finding the 'best fit' of a model to data involves the minimization of a merit function. An example of a merit function is the sum of the squares of the differences between the data points and the model estimated points. This is facilitated by curve-fitting algorithms. Two curve-fitting methods, Levenberg-Marquardt and MINPACK-1, are investigated with respect to the search start points that they require and the accuracy of the returned fits. We have simulated one million dynamic contrast enhanced MRI curves using a range of parameters and investigated the use of single and multiple search starting points. We found that both algorithms, when used with a single starting point, return unreliable fits. When multiple start points are used, we found that both algorithms returned reliable parameters. However the MINPACK-1 method generally outperformed the Levenberg-Marquardt method. We conclude that the use of a single starting point when fitting compartmental modelling data such as this produces unsafe results and we recommend the use of multiple start points in order to find the global minima.

The effects of renal variation upon measurements of perfusion and leakage volume in breast tumours.

Dynamic contrast enhanced MRI (DCE-MRI) and pharmacokinetic models have been used to measure tumour permeability (K(trans)) and leakage volume (ve) in numerous studies. The construction of pharmacokinetic models describing such tissue properties relies on defining the blood plasma concentration of contrast agent with respect to time (Cp(t)). When direct measurement is not possible a bi-exponential decay has been applied using data from healthy volunteers. This work investigates, by simulation, the magnitude of errors resulting from this definition with respect to normal variation in renal function and for cases with renal impairment. Errors up to 23% in ve and 28% in K(trans) were found for the normal simulations, and 67% in ve and 61% in K(trans) for the impaired simulations. If this bi-exponential curve is used as an input function to the generalized kinetic model and used in oncology, estimates of tissue permeability and leakage volume will possess large errors due to variation in Cp(t) curves between subjects.

Novel T*2-weighted contrast preparation scheme for segmented k-space myocardial imaging.

A novel T*(2)-weighted contrast-preparation scheme is described for use with segmented k-space cardiac sequences. This approach frees the imaging phase from the requirement of a long TE and, hence, a relatively long TR. A [90 degrees (x)-tau-90 degrees (rho)] preparation scheme is used to acquire four image data sets with the phase rho of the second pulse set to x, y, -x, and -y. The rho = x raw data is subtracted from the rho = -x data to form the "x" image, with a similar subtraction to generate the "y" image. These images are added in quadrature to obtain the T*(2)-weighted image. The method results in reduced artifact compared to a simple two-image scheme with rho = x, and y. T*(2) was measured in the myocardial septum in six normal volunteers by comparing tau = 7 and 28 ms images, and it was found to be 44 +/- 5 ms at 0.95 T.

The measurement of fetal liver T(*)(2) in utero before and after maternal oxygen breathing: progress towards a non-invasive measurement of fetal oxygenation and placental function.

Utero-placental insufficiency is thought to be a major cause of growth retardation in utero and an important risk factor in the perinatal period. The purpose of this study was to investigate whether MRI could detect changes of fetal oxygenation, based on the blood oxygenation level dependence (BOLD) of the MRI tissue signal. Nine third trimester women (34-38 weeks) with normal pregnancies underwent abdominal MRI examinations. Following localization of the fetal liver using T(2)-weighted single-shot HASTE scans, up to 7 breath-held transaxial single-slice gradient-echo image sets were obtained through the fetal liver. The mother then commenced oxygen breathing with the imaging procedure repeated after 20 minutes of O(2) breathing. For each image set, T(*)(2) values are calculated using linear regression of log (signal) versus TE for a region of interest within the fetal liver selected by the attending radiologist. Fetal liver T(*)(2) values were calculated before and after O(2) breathing for each multi-echo image acquisition set. A signed rank test was used to test for a significant change in fetal liver T(*)(2) between the pre-O(2) and post-O(2) image sets. A significant increase in T*(2) (alpha < 0.05) was seen in 5 of the 9 fetal livers, a smaller increase (of borderline statistical significance, alpha = 0.057) in 2 livers, and no significant change (alpha > 0.05) in 2 livers. Our study indicates that T(*)(2) measurement of the fetal liver may detect alteration in fetal oxygen level following maternal oxygenation using the BOLD effect. This technique may potentially be applied to the identification and understanding of placental dysfunction in intra-uterine growth retardation.