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Background Quantification of physiological parameters, including myocardial blood flow (MBF), by perfusion MRI relies on analysis of data that describes temporal variation of relative contrast agent concentration following bolus administration. At doses required for sufficient SNR, signal enhancement cannot be used directly as the relationship between signal intensity (SI) and the resulting concentrations in blood and myocardium is non-linear. Proposed solutions to this include separation of the AIF and myocardial data acquisition, or model based non-linearity correction.

Methods This was a retrospective study using a 128 patient subsample of patients, selected from the CE-MARC study such that the distribution of risk factors and disease status within the sample was representative of the full study population. Both visual and quantitative analysis were carried out using the AHA standardised 16 segment model. Visual analysis was part of the original CE-MARC study and was performed by 2 expert reviewers in consensus. To obtain qMBF estimates, manual contouring of the myocardium was carried out and individual qMBF estimates were obtained for each AHA segment using Fermi-constrained deconvolution. The arterial input function was taken from the left ventricular blood pool of the basal slice. Myocardial perfusion reserve values were calculated on a segment by segment basis by dividing the stress by the rest qMBF. The reference standard for myocardial ischaemia was a quantitative coronary X-ray angiogram (QCA) score of ≥70% in any of the coronary territories, or ≥50% in the left main stem. Diagnostic performance was calculated using receiver operator characteristic (ROC) curve analysis. For visual analysis the summed score from all AHA segments was used as the diagnostic measure. For quantitative analysis the minimum MPR value from the AHA segments was used. A DeLong, DeLong, ClarkePearson analysis was performed to test for a statistically significant difference in the area under the curve (AUC) values between visual and quantitative analysis.

Background The human interaction required for manual motion correction/contouring of cardiac perfusion series remains a significant obstacle to quantitative perfusion gaining a wider acceptance in clinical practice. The use of image registration for motion correction in perfusion data offers a considerable time saving. Numerous registration methods have been proposed, with evaluation limited to the image registration accuracy. However, the important clinical question is how do these methods affect diagnosis? The aim of this study is to evaluate perfusion series registration in terms of its affect on the diagnostic accuracy of myocardial ischaemia.

Background Type 2 Diabetes Mellitus (T2DM) and prediabetes are associated with an increased cardiovascular risk and heart failure independent of the presence of obstructive coronary artery disease, caused in part by myocardial microvascular dysfunction. Recent studies have reported contractile dysfunction and increased rotation with the onset of diabetic cardiomyopathy in uncomplicated T2DM patients. Independently, higher resting myocardial blood flow (MBF) has been reported in T2DM. The objective of this study was to determine whether there is a correlation between LV Epicardial Rotation (LV ER) and resting MBF in T2DM patients with angiographically normal coronaries, measured by tissue tagging and perfusion cardiovascular Magnetic Resonance (CMR). Methods Sixty five patients with no coronary stenosis >30% on invasive angiography were recruited and categorized into T2DM, prediabetes and normal controls groups according to American Diabetes Association guidelines. All patients underwent rest and adenosine stress myocardial perfusion CMR at a single mid-LV location, cine imaging covering the entire heart and myocardial tissue tagging in three LV short axis locations (apical, mid LV and basal). LV volumes and mass were calculated from cine images. LV rotation in three myocardial layers (endocardial, midmyocardial and epicardial) was calculated from CSPAMM tissue images using Tag Track (Gyrotools, Zurich). For this study, only rest MBF was calculated using Fermi-constrained deconvolution for the entire myocardium. Results Patient characteristics and results are shown in Table 1. Patients with T2DM had significantly higher resting MBF than the two other groups. Corresponding mid LV ER was higher in T2DM patients compared to patients with prediabetes and normal controls (Figure 1) (not statistically significant). Univariate analysis showed a significant positive correlation between MBF and LV ER in the entire study population (Pearson coefficient (r) of 0.25, p = 0.05). In the individual groups, the linear determination coefficient (R2) showed that LV ER in T2DM patients had stronger positive correlation (R2 = 0.31) with resting MBF than in patients with prediabetes (R2 = 0.16) and controls (R2 = 0.29), Figure 1. Conclusions T2DM patients when compared to age-matched patients with prediabetes and normal controls have higher peak LV ER. Resting MBF correlates with LV ER. These results suggest that LV ER analysis in uncomplicated T2DM patients may be useful for non-invasive screening of early subtle contractile dysfunction associated with microvascular dysfunction in diabetes patients.

This study has shown that in patients with suspected and confirmed CAD, estimates of MBF by perfusion-CMR are significantly higher in diastole than systole during maximal hyperemic stress.

Introduction Dynamic contrast enhanced myocardial perfusion MRI (DCE-MRI) has the potential to be superior to other currently available imaging techniques for the assessment of myocardial ischaemia. Quantitative analysis of cardiac perfusion is currently not routinely carried out because of the time consuming process of manually segmenting the myocardium from large DCE-MRI datasets. A range of automated segmentation algorithms have been proposed which quote results in terms of distance error or estimated myocardial blood flow (MBF). However, the relationship between these two evaluation measures is not clear, making objective comparisons of algorithm performance difficult.

Background Diagnostic studies using dynamic contrast enhanced (DCE) MRI perfusion imaging typically evaluate perfusion in terms of the myocardial perfusion reserve (MPR), which is the ratio of stress to rest myocardial blood flow (MBF) measurements. The aim of this study was to establish whether or not, in the case of absolute MBF quantitation, the MPR exhibits a diagnostic advantage over the stress MBF measurements alone.

Methods This was a retrospective sub-study using data from the CE-MARC trial (Greenwood et al., Lancet, 2012). A 50 patient sample of patients were selected such that the distribution of risk factors and disease status within the sample was representative of the full CE-MARC cohort. Quantitative myocardial blood flow (MBF) estimates were obtained from the MRI data using four previously proposed models, commonly used in the quantitative cardiac perfusion literature. These models were: Fermiconstrained deconvolution, model independent deconvolution, the uptake model and the one compartment model. Myocardial Perfusion Reserve (MPR) ratios were calculated from the ratio of stress to rest MBF estimates. The presence of myocardial ischaemia was assessed using the consensus diagnosis of invasive, quantitative X-ray angiography and myocardial Single Photon Computed Tomography (SPECT) imaging. This provided a unique gold-standard combining independent anatomical and functional diagnostic measures. Receiver Operator Characteristic (ROC) curves were generated for each perfusion model using 1) the MPR, and 2) the stress MBF as the diagnostic measure. A DeLong, DeLong, Clarke-Pearson comparison was used to test for statistically significant differences in the Area Under the Curve (AUC) values of the four models.

Background It is generally acknowledged that the 17-segment AHA model provides a suitable approximation for mapping the results of X-ray angiography onto myocardial anatomy in a consistent way in the absence of a more exact method. In practice, coronary anatomy varies from patient to patient which is acknowledged as the main limitation of the AHA model. The aim of this study was to establish whether the generation of a patient-specific coronary artery to perfusion segment map improved diagnosis of myocardial ischaemia.

Background Automated mage registration in cardiac myocardial perfusion is a necessity before quantitative perfusion can be widely accepted in clinical practice. Increasingly complex motion correction algorithms are being developed to deal with cardiac motion. However, the impact of these improvements has not been evaluated in terms of the final clinical diagnosis. Advanced motion correction methods are associated with increased computational overhead and the potential of introducing subtle registration errors, which can be hard to detect and quantify. The aim of this study was to compare the performance of the various automated correction methods in terms of their impact on diagnostic accuracy.

Background This study is the first to use quantitative perfusion CMR to evaluate regional differences in myocardial blood flow (MBF) in patients with left bundle branch block (LBBB). LBBB is often associated with underlying CAD but its presence can limit the diagnostic accuracy of non-invasive imaging tests. In particular, there is a high incidence of false-positive results with exercise SPECT due to apparent septal perfusion defects. The use of vasodilator stress has reduced but not eliminated this problem. Several hypotheses have been postulated to explain the cause of such perfusion defects, and these include early activation of the septum, leading to shortened diastole and reduced blood flow; partial volume effects caused by impaired septal thickening; and increased septal intra-myocardial pressure during diastole, resulting in reduced flow reserve. A number of small studies using PET or early quantitative SPECT techniques have evaluated regional differences in MBF in patients with LBBB, but the results have been conflicting and have shown either no regional differences or a relative but not absolute reduction in septal perfusion. This study re-evaluates the unresolved question of septal perfusion in LBBB using quantitative perfusion CMR.

Background There is an epidemic of obesity and Type-2 Diabetes Mellitus (T2DM) in the developed world. Subclinical diastolic dysfunction in diabetes is associated with the development of overt heart failure. Although diabetic cardiomyopathy is well documented in older adults with T2DM there are scarce data on younger adults and no published CMR data. We aimed to assess the prevalence and potential mechanisms of subclinical left ventricular (LV) dysfunction in young T2DM adults compared to healthy lean (LC) and obese controls (OC). Methods

Type 2 Diabetes Mellitus (T2DM) is associated with an increased risk of heart failure independently of underlying coronary artery disease (CAD) [1]. Myocardial blood flow (MBF) and MBF reserve can be abnormal in patients with T2DM due to myocardial microvascular dysfunction, contributing to the development of heart failure [2]. The myocardial layers may be affected differently by this disease process.

Methods Thirty-nine patients with 3VD at X-ray coronary angiography and 39 matched patients with no significant coronary disease were identified from the CE-MARC study population [1]. Patients were matched by age, gender, hypertension and diabetes. CMR adenosine stress perfusion imaging was undertaken using a saturation-recovery gradient echo pulse sequence producing three image slices per R-R interval. Visual and Fermi deconvolutionderived CMR myocardial perfusion reserve (MPR) analyses were performed. Gated SPECT imaging was performed and interpreted by an experienced observer blinded to other test results.

Background Single bolus quantitative myocardial perfusion is sensitive to systematic errors due to the non-linear relationship between contrast agent concentration and MR signal. These errors can be minimised by using a low dose contrast bolus or by altering the imaging sequence parameters. However, these approaches substantially reduce the contrast to noise ratio of the images increasing the noise in the myocardial blood flow (MBF) values. This study compared two techniques proposed to address these issues; the dual-bolus technique and dualsequence imaging.

Increased endocardial to epicardial flow ratio present at rest disappears during exercise stress perfusion CMR in normal volunteers a potential mechanism for exercise induced subendocardial ischaemia Kaleab N Asrress, Rupert Williams, Tim Lockie, John D Biglands, Amedeo Chiribiri, Aleksandra Radjenovic, Roy Jogiya, Kalpa De Silva, Sebastian Kozerke, Phil Chowienczyk, Eike Nagel, Michael Marber, Simon Redwood, Sven Plein

Background Intramyocardial hemorrhage (IMH) identified by CMR is an established prognostic marker following acute myocardial infarction (AMI), but remains relatively underused in the clinical setting. Detection of IMH by T2-weighted or T2* CMR can be limited by long breath hold times and sensitivity to artefacts, especially at 3 Tesla. Alternative methods that can detect IMH with shorter breath hold times are therefore desirable. CMR is capable of detecting differences in the magnetic susceptibility of tissues. The paramagnetic properties of hemoglobin products within IMH cause local phase shifts relative to surrounding tissue. Phase data can be filtered and combined with magnitude data to generate susceptibility weighted MR images (SW MRI). SW imaging has been shown to be highly sensitive for the detection of cerebral hemorrhage, but typically uses long echo times, resulting in prolonged image acquisition. With the larger size of IMH, we hypothesized that SW MRI may be used with shorter echo times, leading to rapid imaging with breath hold times of approximately 4 seconds. We compared the image quality and diagnostic ability of this SW MRI pulse sequence with T2-weighted and T2* CMR to detect IMH at 3T. Methods

Methods 10 volunteers (7 male, mean age 38 years) were studied on a 1.5 T Philips Intera system during adenosine induced hyperaemia (140 mcg/kg/min for 3 minutes, 0.05 mmol/ kg Gd-DTPA) and at rest. A pulse sequence optimised for acquisition of a single midventricular slice at systole was used (saturation recovery segmented gradient echo, 2 × SENSE TR/TE/flip 2.7 ms/1.0/15°, typical FOV 380 × 380 mm, matrix 160 × 160, slice thickness 10 mm, preparation pulse delay 150 ms, shot duration 130 ms). Endo and epicardial contours were drawn and the slice segmented into 6 equidistant sectors. These were further subdivided into epicardial, mid-myocardial and endocardial thirds. Based on LV and blood pool time intensity curves, an inhouse mathematical Fermi Function deconvolution algorithm was implemented to estimate absolute myocardial blood flow [2].

Summary Dynamic contrast-enhanced (DCE) MRI was performed in 16 healthy subjects to measure myocardial microvascular characteristics. In addition, repeatability was assessed in 11 of those subjects who underwent a second examination. The results showed that Gd-DTPA transport in the myocardium is not perfusion limited at rest or under adenosine stress. Background DCE MRI has been used to estimate myocardial perfusion (blood flow, Fb) but there has been little work published on using this technique to measure related microvascular characteristics, such as microvessel permeability-surface area product (PS) and interstitial volume (extra-vascular extra-cellular volume, ve). The reason may be that transport of Gd-DTPA in resting myocardium is thought to be perfusion limited (with near complete first pass extraction). This study aimed to assess the potential of measuring microvascular characteristics in healthy individuals at rest and under adenosine stress and to assess the repeatability of the measurements.

Methods 11 volunteers (6 males, mean age 33 ± 7 years) underwent CMR perfusion on 2 separate days (mean interstudy delay = 84 ± 111 days, median delay = 7 days) on a 1.5 T Philips Intera system during adenosine-induced hyperaemia (140 mcg/kg/min, 0.05 mmol/kg Gd-DTPA) and rest. A pulse sequence optimised for acquisition of a single midventricular slice at systole was used (saturation recovery segmented gradient echo, 2 × SENSE TR/TE/flip 2.7 ms/1.0/ 15°, typical FOV 380 × 380 mm, matrix 160 × 160, slice thickness 10 mm, preparation pulse delay 150 ms, shot duration 130 ms). Endoand epicardial contours were drawn. "Semi"-quantitative analysis calculated maximal upslopes of myocardial signal intensity of the entire slice, normalised to the LV blood-pool (Myocardial perfusion index, MPI) using MASS 6.0 (Medis, Leiden, The Netherlands). The myocardial perfusion reserve index (MPRI) was calculated as the ratio of hyperaemic over rest MPI.

This is the second of two reviews that is intended to cover the essential aspects of cardiovascular magnetic resonance (CMR) physics in a way that is understandable and relevant to clinicians using CMR in their daily practice. Starting with the basic pulse sequences and contrast mechanisms described in part I, it briefly discusses further approaches to accelerate image acquisition. It then continues by showing in detail how the contrast behaviour of black blood fast spin echo and bright blood cine gradient echo techniques can be modified by adding rf preparation pulses to derive a number of more specialised pulse sequences. The simplest examples described include T2-weighted oedema imaging, fat suppression and myocardial tagging cine pulse sequences. Two further important derivatives of the gradient echo pulse sequence, obtained by adding preparation pulses, are used in combination with the administration of a gadolinium-based contrast agent for myocardial perfusion imaging and the assessment of myocardial tissue viability using a late gadolinium enhancement (LGE) technique. These two imaging techniques are discussed in more detail, outlining the basic principles of each pulse sequence, the practical steps required to achieve the best results in a clinical setting and, in the case of perfusion, explaining some of the factors that influence current approaches to perfusion image analysis. The key principles of contrast-enhanced magnetic resonance angiography (CE-MRA) are also explained in detail, especially focusing on timing of the acquisition following contrast agent bolus administration, and current approaches to achieving time resolved MRA. Alternative MRA techniques that do not require the use of an endogenous contrast agent are summarised, and the specialised pulse sequence used to image the coronary arteries, using respiratory navigator gating, is described in detail. The article concludes by explaining the principle behind phase contrast imaging techniques which create images that represent the phase of the MR signal rather than the magnitude. It is shown how this principle can be used to generate velocity maps by designing gradient waveforms that give rise to a relative phase change that is proportional to velocity. Choice of velocity encoding range and key pitfalls in the use of this technique are discussed.