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Sarcopenia is the loss of muscle size and function during ageing. The aim of this study was to test whether serum concentrations of myostatin and interacting proteins (GASP-1, FLRG, and follistatin) differed between young and elderly sarcopenic men. Isometric knee extensor maximal voluntary contraction and quadriceps cross-sectional area (magnetic resonance imaging measurement) were significantly higher in young (22 ± 2 years; 266 ± 54 N/m; 8,686 ± 1,154 mm(2)) than in mildly sarcopenic (69 ± 3 years; 183 ± 17 N/m; 6,621±718 mm(2)) and severely sarcopenic men (76 ± 6 years; 127 ± 23 N/m; 5,846 ± 591 mm(2)), respectively (p ≤ .01 for all comparisons). There was a trend (p = .06) toward higher FLRG in young (20 ± 8 ng/mL) than in mildly (15 ± 6 ng/mL) and severely sarcopenic men (17 ± 8 ng/mL). Myostatin, follistatin, GASP-1, tumor necrosis factor α, and interleukin-6 did not differ significantly. Insulin-like growth factor-1 and free testosterone were both significantly lower in sarcopenic men (p < .001). This suggests that altered serum concentrations of myostatin and myostatin-interacting proteins are not contributing to sarcopenia with the possible exception of FLRG. [ABSTRACT FROM AUTHOR]

Purpose: To quantify B(1) transmission-field inhomogeneity in breast imaging of normal volunteers at 3T using 3D T(1)-weighted spoiled gradient echo and to assess the resulting errors in enhancement ratio (ER) measured in dynamic contrast-enhanced MRI (DCE-MRI) studies of the breast.Materials and Methods: A total of 25 volunteers underwent breast imaging at 3T and the B(1) transmission-fields were mapped. Gel phantoms that simulate pre- and postcontrast breast tissue T(1) were developed. The effects of B(1)-field inhomogeneity on ER, as measured using a 3D spoiled gradient echo sequence, were investigated by computer simulation and experiments on gel phantoms.Results: It was observed that by using the patient orientation and MR scanner employed in this study, the B(1) transmission-field field is always reduced toward the volunteer's right side. The median B(1)-field in the right breast is reduced around 40% of the expected B(1)-field. For some volunteers the amplitude was reduced by more than 50%. Computer simulation and experiment showed that a reduction in B(1)-field decreases ER. This reduction increases with both B(1)-field error and contrast agent uptake.Conclusion: B(1) transmission-field inhomogeneity is a critical issue in breast imaging at 3T and causes errors in quantifying ER. These errors would be sufficient to reduce the conspicuity of a malignant lesion and could result in reduced sensitivity for cancer detection. [ABSTRACT FROM AUTHOR]

Background: We previously measured the rate of regaining muscle strength during rehabilitation of lower leg muscles in patients following lower leg casting. Our primary aim in this study was to measure the rate of gain of strength in healthy individuals undergoing a similar training regime. Our secondary aim was to test the ability of MRI to provide a biomarker for muscle function., Methods: Men and women were recruited in three age groups: 20-30, 50-65 and over 70 years. Their response to resistance training of the right lower leg twice a week for 8 weeks was monitored using a dynamometer and MRI of tibialis anterior, soleus and gastrocnemius muscles at 2 weekly intervals to measure muscle size (anatomical cross-sectional area ( ACSA )) and quality ( T 2 relaxation). Forty-four volunteers completed the study., Results: Baseline strength declined with age. Training had no effect in middle-aged females or in elderly men in dorsiflexion. Other groups significantly increased both plantarflexion and dorsiflexion strength at rates up to 5.5 N m week -1 in young females in plantarflexion and 1.25 N m week -1 in young males in dorsiflexion. No changes were observed in ACSA or T 2 in any age group in any muscle., Conclusion: Exercise training improves muscle strength in males at all ages except the elderly in dorsiflexion. Responses in females were less clear with variation across age and muscle groups. These results were not reflected in simple MRI measures that do not, therefore, provide a good biomarker for muscle atrophy or the efficacy of rehabilitation., Competing Interests: Competing interests: None declared.

Purpose: To characterize the distribution of bone marrow fat in hip osteoarthritis (OA) using magnetic resonance imaging (MRI) and to assess its use as a potential biomarker., Materials and Methods: In all, 67 subjects (39 female, 28 male) with either total hip replacement (THA) or different severities of radiographic OA, assessed by Kellgren-Lawrence grading (KLG), underwent 3T MRI of the pelvis using the IDEAL sequence to separate fat and water signals. Six regions of interest (ROIs) were identified within the proximal femur. Within each ROI the fractional-fat distribution, represented by pixel intensities, was described by its mean, standard deviation, skewness, kurtosis, and entropy., Results: Hips were graded: 12 as severe symptomatic (THA), 33 had KLG0 or 1, 9 were KLG2, 11 with KLG3, and 2 with KLG4 were analyzed together. The fractional-fat content in the whole proximal femur did not vary with severity in males (mean (SD) 91.2 (6.0)%) but reduced with severity in females from 89.1 (6.7)% (KLG0,1), 91.5 (2.9)% (KLG2), 85.8 (16.7)% (KLG3,4) to 77.5 (11.9)% (THA) (analysis of variance [ANOVA] P = 0.029). These differences were most pronounced in the femoral head, where mean values fell with OA severity in both sexes from 97.9% (2.5%) (KLG0,1) to 73.0% (25.9%) (THA, P < 0.001) with the largest difference at the final stage. The standard deviation and the entropy of the distribution both increased (P < 0.001)., Conclusion: Descriptors of the fractional fat distribution varied little with the severity of OA until the most severe stage, when changes appeared mainly in the femoral head, and have, therefore, limited value as biomarkers., Level of Evidence: 2 J. Magn. Reson. Imaging 2017;45:42-50., (© 2016 International Society for Magnetic Resonance in Medicine.)

Objectives: To compare 3T T1 mapping to conventional T2-weighted (T2W) imaging for delineating myocardial oedema one week after ST-elevation myocardial infarction (STEMI), and to explore the confounding effects of microvascular obstruction (MVO) on each technique., Methods: T2W spectral attenuated inversion recovery and native T1 mapping were applied in 10 healthy volunteers and 62 STEMI patients, and late gadolinium enhancement was included for infarct localisation at 1 week and at 6 months post-STEMI. Segmental T1 values and T2W signal intensity ratios were calculated; oedema volumes and salvage indices were determined in patients using image thresholding-a receiver operator characteristic (ROC) derived T1 threshold, and a 2SD T2W threshold; and the results were compared between patients with/without MVO (n=35/27)., Results: Native T1 mapping delineated oedema with significantly better discriminatory power than T2W-as indicated by ROC analysis (area-under-the-curve, AUC=0.89 versus 0.83, p=0.009; and sensitivity/specificity=83/83% versus 73/73%). The optimal ROC threshold derived for T1 mapping was 1241ms, which gave significantly larger oedema volumes than 2SD T2W (p=0.006); with this threshold, patients with and without MVO showed similar oedema volumes, but patients with MVO had significantly poorer salvage indices (p<0.05) than those without. Neither method was significantly affected by MVO, the volume of which was seen to increase exponentially with infarct size., Conclusions: Native T1 mapping at 3T can delineate oedema one week post-STEMI, showing larger oedema volumes and better discriminatory power than T2W imaging, and it is suitable for quantitative thresholding. Both techniques are robust against MVO-related magnetic susceptibility., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The purpose of this work was to evaluate different magnetization preparation and readout sequences for modified Look-Locker inversion recovery (MOLLI) toward improved T1 mapping in the heart. Elements investigated include: catalyzation sequences to prepare the magnetization before readout, alternate k-space trajectories, a spoiled gradient recalled echo readout, and a 5b(3b)3b MOLLI sampling scheme ('b' denoting beats)., Methods: Conventional 3b(3b)3b(3b)5b MOLLI with a linear k-space trajectory was compared to four variants in simulations, in vitro and in vivo (at 3T). Variants were centric conventional MOLLI, centric-paired conventional MOLLI, linear 5b(3b)3b MOLLI and spoiled gradient recalled echo MOLLI. Each of these was applied with three magnetization catalyzation methods, and T1 measurement accuracy and precision were evaluated in simulations via a Monte Carlo algorithm, in a set of calibrated phantoms, and in ten healthy volunteers. Contrast-to-noise, heart rate dependence and B1+ dependence were also evaluated., Results: A linear k-space trajectory was superior in vitro to centric and centric-paired trajectories. Of the catalyzation methods, preparation of transverse magnetization only-using a linearly increasing flip angle catalyzation-improved MOLLI T1 measurement accuracy, precision, and map quality versus methods that include catalyzation of the longitudinal magnetization. The 5b(3b)3b MOLLI scheme offered comparable native T1 measurement accuracy and precision to conventional MOLLI, despite its shortened acquisition., Conclusions: MOLLI T1 measurement accuracy, precision, and map quality depend on the method of catalyzation of magnetization prior to image acquisition, as well as on the readout method and MOLLI sampling scheme used., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: To examine the relative and combined value of late gadolinium enhancement (LGE) and low-dose dobutamine (LDD) cardiac magnetic resonance (CMR) to predict 'adverse remodelling' (AR) following acute myocardial infarction (AMI)., Methods and Results: Forty-five patients with AMI were recruited. CMR was performed 2-4 days after presentation and at 6 months. Ventricular wall motion and volume were recorded at rest and following dobutamine infusion. Measures of first pass perfusion, persistent microvascular obstruction (PMO), and LGE were obtained following contrast administration. Quantitation was performed using the MEDIS 6.2 software. Regression analysis was employed to determine the univariables and multivariate models most predictive of AR at 6 months. The incremental and relative value of LDD over LGE was investigated. The most predictive univariable was 'volume of PMO' (r = 0.51, r2 = 0.26, P < 0.001). The optimal 'combined' multivariate model, utilizing data from all components, was highly predictive of AR (r = 0.82, r2 = 0.67, P < 0.001). The optimal model using parameters only from the LGE component also predicted remodelling (r = 0.65, r2 = 42.0, P = 0.001) but with less accuracy. In contrast, the optimal model using variables from the LDD component alone predicted remodelling with a similar accuracy to the optimal combined model (r = 0.82, r2 = 0.67, P < 0.001)., Conclusion: A comprehensive CMR examination accurately predicts AR following AMI. LDD is superior to LGE CMR in this respect. These data suggest that LDD not only adds incremental value to LGE in the prediction of remodelling post-AMI but also may be utilized alone with the same predictive power.

Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. Key Points • Tumour vascular function is key to tumour development and treatment • Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascular function • Thus DCE-MRI with pharmacokinetic models can assess novel treatments • Many recent developments are advancing the accuracy of and information from DCE-MRI • Establishing common methodology across multiple centres is challenging and requires accepted guidelines.

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.

An emerging clinical modality called proton magnetic resonance spectroscopy ((1)H-MRS) enables the non-invasive in vivo assessment of tissue metabolism and is demonstrating applications in improving the specificity of MR breast lesion diagnosis and monitoring tumour responsiveness to neoadjuvant chemotherapies. Variations in the concentration of choline-based cellular metabolites, detectable with (1)H-MRS, have shown an association with malignant transformation of tissue in in vivo and in vitro studies. (1)H-MRS exists as an adjunct to the current routine clinical breast MR examination. This review serves as an introduction to the field of breast (1)H-MRS, discusses modern high-field strength and quantitative approaches and technical considerations, and reviews the literature with respect to the application of (1)H-MRS for breast cancer.

Purpose: To investigate MRI biomarkers of muscle atrophy during cast immobilization of the lower leg., Materials and Methods: Eighteen patients (8 male, 10 female), who had one lower leg immobilized in a cast, underwent 3.0 Tesla (T) MR imaging 5, 8, 15, 29, and 43 days after casting. Measurements were made on both lower legs of total muscle volume. Cross-sectional area (CSA), fractional water content, and T(2) were measured in tibialis anterior (TA), gastrocnemius medialis (GM) and lateralis (GL) and soleus (SOL). Fiber pennation angle was measured in GM., Results: Total muscle volume decreased by 17% (P < 0.001) over the 6 weeks of immobilization. The greatest loss in CSA (mean[SD]) was seen in GM (-23.3(8.7)%), followed by SOL (-19.0(9.8)%), GL (-17.1(6.5)%), and TA (-10.7(5.9)%). Significant reductions of CSA were also detectable in the contra-lateral leg. T(2) increased in all muscles: TA 27.0(2.5) ms to 29.6(2.8) ms (P < 0.001), GM 34.6(2.9) ms to 39.8(5.4) ms (P < 0.001) and SOL 34.4 (2.9) ms to 44.9(5.9) ms (P < 0.001). Small reductions were found in fractional water content. Pennation angle decreased in the cast leg (P < 0.001)., Conclusion: Quantitative MR imaging can detect and monitor progressive biochemical and biophysical changes in muscle during immobilization., (Copyright © 2011 Wiley-Liss, Inc.)

The variation of the native T(1) (T(10)) of different tissues and B(1) transmission-field inhomogeneity at 3 T are major contributors of errors in the quantification of breast dynamic contrast-enhanced MRI. To address these issues, we have introduced new enhancement indices derived from saturation-recovery snapshot-FLASH (SRSF) images. The stability of the new indices, i.e., the SRSF enhancement factor (EF(SRSF)) and its simplified version (EF'(SRSF)) with respect to differences in T(10) and B(1) inhomogeneity was compared against a typical index used in breast dynamic contrast-enhanced MRI, i.e., the enhancement ratio (ER), by using computer simulations. Imaging experiments with Gd-DTPA-doped gel phantoms and a female volunteer were also performed. A lower error was observed in the new indices compared to enhancement ratio in the presence of typical T(10) variation and B(1) inhomogeneity. At changes of relaxation rate (ΔR(1)) of 8 s(-1), the differences between a T(10) of 1266 and 566 ms are <1, 12, and 58%, respectively, for EF(SRSF), EF'(SRSF), and ER, whereas differences of 20, 8, and 51%, respectively, result from a 50% B(1) field reduction at the same ΔR(1). These quantification techniques may be a solution to minimize the effect of T(10) variation and B(1) inhomogeneity on dynamic contrast-enhanced MRI of the breast at 3 T., (Copyright © 2011 Wiley Periodicals, Inc.)

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 motivation of the project was to investigate the use of oxygen-challenge magnetic resonance imaging (OC-MRI) as a method of diagnosing foetal growth restriction. Foetal growth restriction is associated with restricted foetal oxygen supply and is also associated with increased risks of perinatal mortality and morbidity, and a number of serious and chronic health problems. Measurements of T2* relaxation time, an MRI parameter which increases with blood oxygenation, were made in the right lobe of the foetal liver in 80 singleton pregnancies, before and after the mother breathed oxygen. The groups consisted of 41 foetuses with normal growth and 39 with apparent growth restriction. The mean +/- SD gestational age at scanning was 35 +/- 3 weeks. Changes in foetal liver T2* on maternal oxygen breathing showed no significant difference between the groups therefore the OC-MRI protocol used in this study has no value in the diagnosis of foetal growth restriction. A secondary finding was that a significant positive correlation of T2* change with gestational age was observed. Future studies on the use of oxygen-challenge MRI to investigate foetal growth restriction may therefore need to control for gestational age at the time of MR scanning in order to observe any underlying foetal growth-related effects.

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.

Background: The different levels of deoxyhemoglobin in the ischemic myocardium, induced by stressors such as dipyridamole, can be detected by blood oxygen level-dependent (BOLD) MRI and may be used to diagnose myocardial ischemia. The aim of this study was to assess the signal change in the myocardium on BOLD MRI as well as wall thickening between rest and dipyridamole stress images in ischemic and non-ischemic myocardium as identified on SPECT imaging., Methods: Twelve patients with stress-induced myocardial ischemia on SPECT underwent rest and dipyridamole stress MRI using a double breath-hold, T2()-weighted, ECG-gated sequence to produce BOLD contrast images as well as cine-MRI for wall thickening assessment in 10 of the 12 patients. Signal change on BOLD MRI and wall thickening were compared between rest and stress images in ischemic and non-ischemic myocardial segments as identified on SPECT. In each patient, two MRI slices containing 16 segments per slice were analysed., Results: In total, there were 384 segments for BOLD analysis and 320 for wall thickening. For BOLD signal 137 segments correlated to segments with reversible ischemia on SPECT and 247 to normal segments, while for wall thickening 112 segments correlated to segments with reversible ischemia and 208 to normal segments. The average BOLD MRI signal intensity change was -13.8 (+/-16.3)% in the ischemic segments compared to -10.3 (+/-14.7)% in the non-ischemic segments (p=0.05). The average wall thickening was 6.4 (+/-3.4) mm in the ischemic segments compared to 8.7 (+/-3.8) mm in the non-ischemic segments (p<0.0001)., Conclusion: Stress-induced ischemic myocardium has a different signal change and wall thickening than non-ischemic myocardium and may be differentiated on BOLD MRI. Larger studies are needed to define a threshold for detection and to determine the sensitivity and specificity of this technique.

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.

Background: The aim of the current study was to assess the utility of transmurality of delayed enhancement on cardiac magnetic resonance imaging (MRI) in predicting functional recovery in patients with first ST-elevation myocardial infarction (MI) who had received thrombolysis., Methods: Nineteen patients underwent cine and contrast-enhanced MRI 3 days and 8 weeks after MI. The transmural extent of infarction (TEI) was determined from the late enhancement component of the first scan. Segmental wall thickening was scored from the cine components of both the initial and follow-up scans., Results: The TEI was inversely related to the likelihood of improvement in wall thickening; chi(2) test for trend = 53.9, p < 0.0001. Delayed enhancement with >50% transmurality predicted a lack of recovery with 82% sensitivity and 54% specificity. The equivalent values for >75% transmurality were 57 and 77%, respectively. The proportion of the left ventricular segments exhibiting functional recovery was related to the percentage of the left ventricle that was severely dysfunctional but had

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.

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 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 objective of this study was to investigate the relationship between vascular and metabolic characteristics of breast tumours in vivo, using contrast-enhanced dynamic MRI and 2-[(18)F] fluoro-2-deoxy- d-glucose (FDG) PET imaging. Twenty patients with large or locally advanced primary breast cancers were imaged prior to therapy. MRI data were acquired using a dynamic gradient echo sequence and analysed using two pharmacokinetic models. Static PET data were acquired in 2D mode. A significant association ( P<0.05) was observed between the calculated exchange rate constants of both pharmacokinetic models and calculated PET FDG dose uptake ratios (DUR). Statistical analysis showed that the exchange rate constants can explain between 27 and 44% of the variance observed in the PET FDG uptake ratios. A relationship was demonstrated between the vascular and metabolic characteristics of primary breast tumours showing that any assessment of tumour metabolic activity using PET may be controlled at least in part by delivery of uptake agent due to the vascular characteristics of the tumour. MRI and PET provide methods of assessing breast tumour vascularity and metabolism in vivo using the exchange rate constants of dynamic MRI, and DUR of PET, respectively, these measures being related but not equivalent.

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.

Brain activation studies offer valuable techniques for exploring human cognition to complement behavioral measures and several studies report a wide range of neuroanatomical networks activated during verbal immediate memory. Behavioral investigations have shown use of multiple cognitive strategies across and within individuals, although aggregate data appear to reflect a common cognitive function. Variation in cognitive strategies could result in aggregate activation patterns that are relatively widespread and difficult to interpret. Imaging data (fMRI) from six participants instructed to use subvocal rehearsal showed significant left hemisphere activation in the inferior parietal gyrus and inferior and middle frontal gyri, a pattern of activation more clearly focused than in previous brain activation studies of immediate verbal serial ordered recall. Our results should be relatively free of the influence of other mental operations, and emphasise the importance of considering which cognitive strategies might give rise to focused or to diverse patterns of brain activation.

Background: The identification of viable myocardium in patients with impaired left ventricular contraction secondary to coronary heart disease is important clinically as such myocardium is likely to benefit from revascularisation. Blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) relies on changes in deoxyhaemoglobin concentration under stress for signal generation and could be used for the differentiation between scarred and viable myocardium., Aim: To assess the signal change on BOLD MRI in viable and scarred myocardium as identified by positron emission tomography (PET)., Method: 19 patients with impaired left ventricular contraction and at least one akinetic area were enrolled. They underwent rest and dipyridamole stress MRI, using a double breath hold T2* weighted, ECG gated sequence to produce BOLD contrast images, and cine-MRI for wall thickening assessment. Dynamic perfusion and metabolic PET images followed the MRI. Signal change on BOLD MRI and the wall thickening were compared between rest and stress images in hibernating and scarred segments identified by PET on two short axis slices of mid ventricle, with eight segments each., Results: Using PET, 68 segments were identified as hibernating and 42 as scarred. The hibernating segments were found on BOLD MRI to have an average signal change between rest and stress of -9.53%, compared with -2.15% in the scarred segments (p = 0.008). The average wall thickening was 8.7 mm in the hibernating segments compared with 5.9 mm in the scarred segments (p < 0.0001)., Conclusions: BOLD MRI with wall thickening may differentiate scarred and viable myocardium and help identify suitable patients for revascularisation. Further larger studies are needed to establish a threshold for detection, sensitivity, and specificity.

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., (Copyright 2003 Wiley-Liss, Inc.)

For accurate and safe placement of dental implants, and planning of associated surgery, a full assessment of the surgical anatomy of the site is necessary. Thus, it is highly desirable to have tomographic, sectional information available, to permit the implant to be aligned correctly. In recent years, X-ray computed tomography (CT) has become accepted as the gold standard in assessment, but the exposure to ionising radiation can be substantial. Artefacts due to dental restorations can also be significant, and some doubts may exist over the accuracy of reformatted CT. Magnetic resonance imaging (MRI) entails no exposure to ionising radiation, and allows direct acquisition of tomographic information in any desired plane. Sequential studies may be safely performed, allowing us a valuable insight into bone graft behaviour. Other than in a small number of cases, MRI may be safely used for presurgical assessments. Artefacts are few and in most cases localised. The surgical confidence from the sectional information gained is a significant step forward in the safe placement of dental implants.

Axillary lymph node status is the most important prognostic factor in breast cancer patients and is currently determined by surgical dissection. This study was performed to assess whether dynamic gadopentetate dimeglumine (Gd) enhanced MRI is an accurate method for non-invasive staging of the axilla. 47 women with a new primary breast cancer underwent pre-operative dynamic Gd enhanced MRI of the ipsilateral axilla. Lymph node enhancement was quantitatively analysed using a region of interest method. Enhancement indices and nodal area were compared with histopathology of excised nodes using a receiver operating characteristic (ROC) curve approach. 10 patients had axillary metastases pathologically and all had > or =1 lymph node with an enhancement index of >21% and a nodal area of >0.4 cm(2). 37 patients had negative axillary nodes pathologically. 20 of these had enhancement indices <21% and nodal areas <0.4 cm(2). Using this method, a sensitivity of 100%, a specificity of 56%, a positive predictive value of 38% and a negative predictive value of 100% could be achieved. Using this method of quantitative assessment, dynamic Gd enhanced MRI may be a reliable method of predicting absence of axillary nodal metastases in women with breast cancer, thereby avoiding axillary surgery in women with a negative MRI study.

Various materials have been used for bone grafts in the sinus lift operation, to increase the vertical bone height in the maxilla before the placement of dental implants in the atrophic maxilla. In this case history, Surgicel (oxidised regenerated cellulose) was used as a graft material for one patient, allowing successful delayed implant placement within new and existing bone. The sinus region was examined three months after grafting with Surgicel using magnetic resonance imaging (MRI). The MR images showed that material of similar MR signal to bone had formed within the graft. MRI allowed us to gain tomographic information of the region without exposure of the patient to ionising radiation. The formation of bone within the Surgicel matrix was confirmed at implant placement. This poses interesting questions as to the physiology of bone formation within non-particulate graft material, warranting further investigation.

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.

In planning placement of dental implants using MRI, a SPAMM (spatial modulation of magnetization) magnetization preparation sequence was incorporated into a spin-echo imaging sequence. A phantom was imaged with a ferromagnetic object attached. Spatial distortion due to deviations in Larmor frequency was detected by a deviation of SPAMM lines. Both SPAMM line deviation and interline spacing were found to agree with a deltaB0 map generated from phase images. Imaging of a volunteer with and without typically used metallic implants positioned in a template showed SPAMM line deviations to correlate with expected deviations in vivo. SPAMM lines showed possible distortion due to chemical shift in the bone marrow and the presence of titanium implants to be insignificant. SPAMM may thus be used to provide a qualitative estimate of the accuracy of the MRI image when planning dental implants.

Objective: To determine how partial removal of the nucleus changes the response of the annulus to compression., Design: The deformation of the annulus in the mid-sagittal plane, during compression, was determined from digital video images., Background: Several studies have shown that removal of the nucleus changes the external behaviour of the intervertebral disc, but few studies have investigated changes to internal behaviour., Methods: Six frozen human lumbar discs were bisected in the sagittal plane to produce 12 specimens. The cut surfaces were marked with seven dots of Alcian blue stain. The specimens were sealed, enabling their internal structure to be viewed directly by a digital video recording system, and thawed. The video system recorded the response of each specimen as it was compressed by up to 1.8 mm at a rate of 0.2 mm s(-1). The displacements of the Alcian blue marks were measured using an image analysis program. Magnetic resonance imaging was used to investigate the validity of this technique., Results: Partial removal of the nucleus changed the way that the disc deformed under compression. A highly significant change in direction of movement was seen in the inner posterior region of the annulus., Conclusions: Partial removal of the nucleus changes the response of the annulus to compression., Relevance: Partial denucleation of the human intervertebral disc is shown to change the direction of bulging of the inner annulus when the disc is compressed. Increases in shear stress, arising from these changes, may lead to further disc degeneration in the form of circumferential tears.

The imaging and analysis protocol of the UK multicentre study of magnetic resonance imaging (MRI) as a method of screening for breast cancer in women at genetic risk is described. The study will compare the sensitivity and specificity of contrast-enhanced MRI with two-view x-ray mammography. Approximately 500 women below the age of 50 at high genetic risk of breast cancer will be recruited per year for three years, with annual MRI and x-ray mammography continuing for up to 5 years. A symptomatic cohort will be measured in the first year to ensure consistent reporting between centres. The MRI examination comprises a high-sensitivity three-dimensional contrast-enhanced assessment, followed by a high-specificity contrast-enhanced study in equivocal cases. Multiparametric analysis will encompass morphological assessment, the kinetics of contrast agent uptake and determination of quantitative pharmacokinetic parameters. Retrospective analysis will identify the most specific indicators of malignancy. Sensitivity and specificity, together with diagnostic performance, diagnostic impact and therapeutic impact will be assessed with reference to pathology, follow-up and changes in diagnostic certainty and therapeutic decisions. Mammography, lesion localisation, pathology and cytology will be performed in accordance with the UK NHS Breast Screening Programme quality assurance standards. Similar standards of quality assurance will be applied for MR measurements and evaluation.

Objectives: To calculate sinus and bone graft volumes and vertical bone heights from sequential magnetic resonance imaging (MRI) examinations in patients undergoing a sinus lift operation., Methods: MRI scans were obtained pre-operatively and at 10 days and 10 weeks post-operatively, using a 0.95 tesla MRI scanner and a three-dimensional (3D) magnetisation prepared, rapid acquisition gradient-echo (MP-RAGE) sequence., Results: Estimates of the bone graft volumes required for a desired vertical bone height were made from the pre-operative MRI scan. Measurements of the graft volumes and bone heights actually achieved were made from the post-operative scans. The MRI appearance of the graft changed between the 10 day and 10 week scans., Conclusions: We have proposed a technique which has the potential to give the surgeon an estimate of the optimum volume of graft for the sinus lift operation from the pre-operative MRI scan alone and demonstrated its application in a single patient. Changes in the sequential MRI appearance of the graft are consistent with replacement of fluid by a matrix of trabecular bone.

Aim: Inflammatory abdominal aortic aneurysms (IAAA) are a variant of abdominal aortic aneurysms, which are associated with an increased morbidity. The diagnosis of IAAA has traditionally been established with a combination of clinical and laboratory findings together with contrast enhanced CT. There is a high incidence of renal impairment in this group, and therefore contrast enhanced CT may be harmful., Patients and Methods: Five patients with IAAA underwent T1-weighted spin echo and gradient echo gadolinium enhanced abdominal MRI. A total of eight examinations were performed, including three patients who underwent repeat MRI following steroid therapy., Results: The inflammatory cuff was clearly identified following gadolinium administration in all eight examinations. The cuff enhanced homogeneously in all patients with no alteration in appearance following steroid therapy. The intravenous administration of gadolinium DTPA enabled clearer definition of locally involved structures., Conclusion: Gadolinium enhanced MRI readily demonstrates features of IAAA. In view of potential renal impairment in this patient group, we recommend this technique in preference to contrast enhanced CT in the initial investigation of inflammatory abdominal aortic aneurysms., (Copyright 2000 The Royal College of Radiologists.)

The inverse relationship between the radiofrequency (RF) power needed to transmit a 90 degree RF pulse, and the signal-to-noise ratio (SNR) available from a transmit-receive RF coil is well known. The theory is restated and a formula given for the signal-to-noise ratio from water, achievable from a single-shot MRI experiment, in terms of the net forward RF power needed for a rectangular 90 degree RF pulse of known shape and duration. The result is normalized to a signal bandwidth of 1 Hz and a sample mass of 1 g. The RF power information needed is available on most commercial scanners, as it is used to calculate specific absorption rates for RF tissue heating. The achievable SNR figure will normally be larger that that actually observed, mainly because of receiver noise, but also because of inaccuracies in setting RF pulse angles, and relaxation effects. Phantom experiments were performed on the transmit-receive RF head coil of a commercial MRI system at 0.95 T using a projection method. The measured SNR agreed with that expected from the formula for achievable SNR once a correction was made for the noise figure of the receiving chain. Comparisons of measured SNR figures with those calculated from RF power measurements are expected to be of value in acceptance testing and quality control.

Objective: To assess the use of dobutamine magnetic resonance imaging (MRI) as a preoperative predictor of myocardial functional recovery after revascularisation, comparing wall motion and radial wall thickening analyses by observer and semi-automated edge detection., Patients: 25 men with multivessel coronary disease and resting wall motion abnormalities were studied with preoperative rest and stress MRI., Main Outcome Measures: Observer analysis for radial wall thickening was compared with a normal range, while wall motion analysis used a standard four point scale. Semi-automated analysis was performed using an edge detection algorithm. Segments displaying either improved or worsened thickening or motion with dobutamine were considered viable. Postoperative rest images were performed 3-6 months after coronary artery bypass grafting (CABG) for comparison., Results: For observer analysis the values for sensitivity and specificity were 50% and 72% for wall motion, with respective values of 50% and 68% for thickening. With semi-automated edge detection the figures for motion were 60% and 73%, with corresponding values of 79% and 58% for thickening. Combining thickening and motion for the semi-automated method to describe any change in segmental function yielded a sensitivity of 71% and specificity of 70%., Conclusions: Dobutamine MRI is a reasonably good predictor of myocardial functional recovery after CABG. The use of semi-automated edge detection analysis improved results.

Sinus lift operations are done to increase bone thickness before placement of osseointegrated implants in areas of the maxilla where there is insufficient bone between the lower border of the maxillary sinus mucosa and the oral mucoperiosteum. Full sectional information should be available to the surgeon before the sinus lift operation so that the outcome can be predicted, and to allow for assessment of the volume of bone graft required. It is also useful to assess the success of the procedure before placement of the implant, and to choose the implant length and orientation required for maximum stability. We describe the use of a 0.2 tesla magnetic resonance imaging (MRI) scanner to image a patient before and after sinus lift. MRI gave full sectional information of the bone on both occasions without using ionizing radiation. The quality of the images was good, and should be considered as an alternative to the accepted gold standard of computed tomography (CT), which exposes the patient to a high dose of radiation.

Difficulties in obtaining diffusion-weighted images of acceptable quality using conventional hardware and in a reasonable time have hindered the clinical application of diffusion-weighted magnetic resonance imaging (DWI). Diffusion-weighted fast spin-echo (FSE) sequences offer the possibility of fast DWI on standard hardware without the susceptibility problems associated with echoplanar imaging. However, motion in the presence of diffusion-sensitizing gradients can prevent fulfilment of the Meiboom Gill phase condition, leading to destructive interference between echo components and consequent signal losses. A recently proposed single-shot FSE sequence employed split-echo acquisition to address this problem. However, in a segmented FSE sequence, phase errors differ between successive echo trains, causing "ghosting" in the diffusion-weighted images that are not eliminated by split-echo acquistion alone. A DWI technique is presented that combines split-echo acquisition with navigator echo phase correction in a segmented FSE sequence. It is shown to be suitable for diffusion measurements in vivo using standard hardware.

In vivo T1 measurements, used to monitor the uptake of contrast agent by tissues, are typically performed as a first step in implementing compartmental analysis of contrast-enhanced breast magnetic resonance imaging (MRI) data. We have extended previously described methodology for in vivo T1 measurement (using a variable flip-angle gradient-recalled echo technique) to two-dimensional (2D), fast low-angle shot (FLASH). This approach requires computational modeling of slice-selective radiofrequency (RF) excitation to correct for nonrectangular slice profiles. The accuracy with which breast tissue T1 values can be measured by this approach is examined: T1 measurements from phantom and in vivo image data acquired with 2D and 3D FLASH imaging sequences are presented. Significant sources of error due to imaging pulse sequence quality and RF transmit field nonuniformity in the breast coil device that will have detrimental consequences for compartmental analysis are identified. Rigorous quality assurance programs with calibrated phantoms are thus recommended, to verify the accuracy with which T1 measurements are obtained.

Snapshot FLASH preceded by a preparation sequence is used to measure NMR parameters. Some preparation information is lost during snapshot FLASH acquisition as the magnetization evolves towards the steady state. This problem is often addressed by assuming that image intensity is proportional to the central k-space line, which may be sampled immediately after preparation using a centric-reordered scheme. Although some limitations of this assumption have been discussed, they are often ignored in parameter measurement. In this study, magnetization evolution effects in snapshot FLASH were investigated by computer simulation and phantom experiments in the context of T2 measurement. It was found that the standard analysis may lead to significant error in parameter measurement. Some improvement may be obtained using a more sophisticated analysis to take account of magnetization evolution. However, at the expense of a 50% reduction in signal intensity, accurate values may be obtained by a novel method that uses crusher gradients to eliminate evolved magnetization.

A semi-automated edge detection method for the delineation of the endo- and epicardial borders of the left ventricle from cine MR images has been developed. The feasibility of this was demonstrated by processing end diastolic and end systolic ECG-gated images of four short axis images in 10 healthy subjects. The first derivative method combined with a 2D weighted polynomial fitting procedure was used to determine the endo- and epicardial borders, which then allowed determination of the wall motion, wall thickening, and ejection fraction, of the left ventricle. The results show that the end-systolic radial wall motion varies from (32+/-8)% to (76+/-12)%, and wall thickening from (0.60+/-0.46) cm to (1.26+/-0.50) cm. An average ejection fraction of (69+/-6)% was found which agrees well with literature values. The method described, for the delineation of the borders, reduces considerably the long and tedious operator time inherent in manual measurement and greatly increases the reproducibility of the measurements.