Peter Kellman

Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement

Rapid innovations in cardiovascular magnetic resonance (CMR) now permit the routine acquisition of quantitative measures of myocardial and blood T1 which are key tissue characteristics. These capabilities introduce a new frontier in cardiology, enabling the practitioner/investigator to quantify biologically important myocardial properties that otherwise can be difficult to ascertain clinically. CMR may be able to track biologically important changes in the myocardium by: a) native T1 that reflects myocardial disease involving the myocyte and interstitium without use of gadolinium based contrast agents (GBCA), or b) the extracellular volume fraction (ECV)–a direct GBCA-based measurement of the size of the extracellular space, reflecting interstitial disease. The latter technique attempts to dichotomize the myocardium into its cellular and interstitial components with estimates expressed as volume fractions. This document provides recommendations for clinical and research T1 and ECV measurement, based on published evidence when available and expert consensus when not. We address site preparation, scan type, scan planning and acquisition, quality control, visualisation and analysis, technical development. We also address controversies in the field. While ECV and native T1 mapping appear destined to affect clinical decision making, they lack multi-centre application and face significant challenges, which demand a community-wide approach among stakeholders. At present, ECV and native T1 mapping appear sufficiently robust for many diseases; yet more research is required before a large-scale application for clinical decision-making can be recommended.

Phase-sensitive inversion recovery for detecting myocardial infarction using gadolinium-delayed hyperenhancement.

After administration of gadolinium, infarcted myocardium exhibits delayed hyperenhancement and can be imaged using an inversion recovery (IR) sequence. The performance of such a method when using magnitude‐reconstructed images is highly sensitive to the inversion recovery time (TI) selected. Using phase‐sensitive reconstruction, it is possible to use a nominal value of TI, eliminate several breath‐holds otherwise needed to find the precise null time for normal myocardium, and achieve a consistent contrast. Phase‐sensitive detection is used to remove the background phase while preserving the sign of the desired magnetization during IR. Experimental results are presented which demonstrate the benefits of both phase‐sensitive IR image reconstruction and surface coil intensity normalization for detecting myocardial infarction (MI). The phase‐sensitive reconstruction method reduces the variation in apparent infarct size that is observed in the magnitude images as TI is changed. Phase‐sensitive detection also has the advantage of decreasing the sensitivity to changes in tissue T1 with increasing delay from contrast agent injection. Magn Reson Med 47:372–383, 2002. Published 2002 Wiley‐Liss, Inc.

Adaptive sensitivity encoding incorporating temporal filtering (TSENSE).

A number of different methods have been demonstrated which increase the speed of MR acquisition by decreasing the number of sequential phase encodes. The UNFOLD technique is based on time interleaving of k‐space lines in sequential images and exploits the property that the outer portion of the field‐of‐view is relatively static. The differences in spatial sensitivity of multiple receiver coils may be exploited using SENSE or SMASH techniques to eliminate the aliased component that results from undersampling k‐space. In this article, an adaptive method of sensitivity encoding is presented which incorporates both spatial and temporal filtering. Temporal filtering and spatial encoding may be combined by acquiring phase encodes in an interleaved manner. In this way the aliased components are alternating phase. The SENSE formulation is not altered by the phase of the alias artifact; however, for imperfect estimates of coil sensitivities the residual artifact will have alternating phase using this approach. This is the essence of combining temporal filtering (UNFOLD) with spatial sensitivity encoding (SENSE). Any residual artifact will be temporally frequency‐shifted to the band edge and thus may be further suppressed by temporal low‐pass filtering. By combining both temporal and spatial filtering a high degree of alias artifact rejection may be achieved with less stringent requirements on accuracy of coil sensitivity estimates and temporal low‐pass filter selectivity than would be required using each method individually. Experimental results that demonstrate the adaptive spatiotemporal filtering method (adaptive TSENSE) with acceleration factor R = 2, for real‐time nonbreath‐held cardiac MR imaging during exercise induced stress are presented. Magn Reson Med 45:846–852, 2001. Published 2001 Wiley‐Liss, Inc.

Image reconstruction in SNR units : A general method for SNR measurement

The method for phased array image reconstruction of uniform noise images may be used in conjunction with proper image scaling as a means of reconstructing images directly in SNR units. This facilitates accurate and precise SNR measurement on a per pixel basis. This method is applicable to root‐sum‐of‐squares magnitude combining, B1‐weighted combining, and parallel imaging such as SENSE. A procedure for image reconstruction and scaling is presented, and the method for SNR measurement is validated with phantom data. Alternative methods that rely on noise only regions are not appropriate for parallel imaging where the noise level is highly variable across the field‐of‐view. The purpose of this article is to provide a nuts and bolts procedure for calculating scale factors used for reconstructing images directly in SNR units. The procedure includes scaling for noise equivalent bandwidth of digital receivers, FFTs and associated window functions (raw data filters), and array combining. Magn Reson Med, 2005. Published 2005 Wiley‐Liss, Inc.

Association Between Extracellular Matrix Expansion Quantified by Cardiovascular Magnetic Resonance and Short-Term Mortality

Background— Extracellular matrix expansion may be a fundamental feature of adverse myocardial remodeling, it appears to be treatable, and its measurement may improve risk stratification. Yet, the relationship between mortality and extracellular matrix is not clear because of difficulties with its measurement. To assess its relationship with outcomes, we used novel, validated cardiovascular magnetic resonance techniques to quantify the full spectrum of extracellular matrix expansion not readily detectable by conventional cardiovascular magnetic resonance. Methods and Results— We recruited 793 consecutive patients at the time of cardiovascular magnetic resonance without amyloidosis or hypertrophic cardiomyopathy as well as 9 healthy volunteers (ages 20–50 years). We measured the extracellular volume fraction (ECV) to quantify the extracellular matrix expansion in myocardium without myocardial infarction. ECV uses gadolinium contrast as an extracellular space marker based on T1 measures of blood and myocardium pre— and post–gadolinium contrast and hematocrit measurement. In volunteers, ECV ranged from 21.7% to 26.2%, but in patients it ranged from 21.0% to 45.8%, indicating considerable burden. There were 39 deaths over a median follow-up of 0.8 years (interquartile range 0.5–1.2 years), and 43 individuals who experienced the composite end point of death/cardiac transplant/left ventricular assist device implantation. In Cox regression models, ECV related to all-cause mortality and the composite end point (hazard ratio, 1.55; 95% confidence interval, 1.27–1.88 and hazard ratio, 1.48; 95% confidence interval, 1.23–1.78, respectively, for every 3% increase in ECV), adjusting for age, left ventricular ejection fraction, and myocardial infarction size. Conclusions— ECV measures of extracellular matrix expansion may predict mortality as well as other composite end points (death/cardiac transplant/left ventricular assist device implantation).

T1-mapping in the heart: accuracy and precision

The longitudinal relaxation time constant (T1) of the myocardium is altered in various disease states due to increased water content or other changes to the local molecular environment. Changes in both native T1 and T1 following administration of gadolinium (Gd) based contrast agents are considered important biomarkers and multiple methods have been suggested for quantifying myocardial T1 in vivo. Characterization of the native T1 of myocardial tissue may be used to detect and assess various cardiomyopathies while measurement of T1 with extracellular Gd based contrast agents provides additional information about the extracellular volume (ECV) fraction. The latter is particularly valuable for more diffuse diseases that are more challenging to detect using conventional late gadolinium enhancement (LGE). Both T1 and ECV measures have been shown to have important prognostic significance.T1-mapping has the potential to detect and quantify diffuse fibrosis at an early stage provided that the measurements have adequate reproducibility. Inversion recovery methods such as MOLLI have excellent precision and are highly reproducible when using tightly controlled protocols. The MOLLI method is widely available and is relatively mature. The accuracy of inversion recovery techniques is affected significantly by magnetization transfer (MT). Despite this, the estimate of apparent T1 using inversion recovery is a sensitive measure, which has been demonstrated to be a useful tool in characterizing tissue and discriminating disease. Saturation recovery methods have the potential to provide a more accurate measurement of T1 that is less sensitive to MT as well as other factors. Saturation recovery techniques are, however, noisier and somewhat more artifact prone and have not demonstrated the same level of reproducibility at this point in time.This review article focuses on the technical aspects of key T1-mapping methods and imaging protocols and describes their limitations including the factors that influence their accuracy, precision, and reproducibility.

T2-prepared SSFP improves diagnostic confidence in edema imaging in acute myocardial infarction compared to turbo spin echo.

T2‐weighted MRI of edema in acute myocardial infarction (MI) provides a means of differentiating acute and chronic MI, and assessing the area at risk of infarction. Conventional T2‐weighted imaging of edema uses a turbo spin‐echo (TSE) readout with dark‐blood preparation. Clinical applications of dark‐blood TSE methods can be limited by artifacts such as posterior wall signal loss due to through‐plane motion, and bright subendocardial artifacts due to stagnant blood. Single‐shot imaging with a T2‐prepared SSFP readout provides an alternative to dark‐blood TSE and may be conducted during free breathing. We hypothesized that T2‐prepared SSFP would be a more reliable method than dark‐blood TSE for imaging of edema in patients with MI. In patients with MI (22 acute and nine chronic MI cases), T2‐weighted imaging with both methods was performed prior to contrast administration and delayed‐enhancement imaging. The T2‐weighted images using TSE were nondiagnostic in three of 31 cases, while six additional cases rated as being of diagnostic quality yielded incorrect diagnoses. In all 31 cases the T2‐prepared SSFP images were rated as diagnostic quality, correctly differentiated acute or chronic MI, and correctly determined the coronary territory. Free‐breathing T2‐prepared SSFP provides T2‐weighted images of acute MI with fewer artifacts and better diagnostic accuracy than conventional dark‐blood TSE. Magn Reson Med 57:891–897, 2007. Published 2007 Wiley‐Liss, Inc.

Myocardial Edema as Detected by Pre-Contrast T1 and T2 CMR Delineates Area at Risk Associated With Acute Myocardial Infarction

OBJECTIVES The aim of this study was to determine whether cardiac magnetic resonance (CMR) in vivo T1 mapping can measure myocardial area at risk (AAR) compared with microspheres or T2 mapping CMR. BACKGROUND If T2-weighted CMR is abnormal in the AAR due to edema related to myocardial ischemia, then T1-weighted CMR should also be able to detect and accurately quantify AAR. METHODS Dogs (n = 9) underwent a 2-h coronary occlusion followed by 4 h of reperfusion. CMR of the left ventricle was performed for mapping of T1 and T2 prior to any contrast administration. AAR was defined as regions that had a T1 or T2 value (ms) >2 SD from remote myocardium, and regions with microsphere blood flow (ml/min/g) during occlusion <2 SD from remote myocardium. Infarct size was determined by triphenyltetrazolium chloride staining. RESULTS The relaxation parameters T1 and T2 were increased in the AAR compared with remote myocardium (mean ± SD: T1, 1,133 ± 55 ms vs. 915 ± 33 ms; T2, 71 ± 6 ms vs. 49 ± 3 ms). On a slice-by-slice basis (n = 78 slices), AAR by T1 and T2 mapping correlated (R(2) = 0.95, p < 0.001) with good agreement (mean ± 2 SD: 0.4 ± 16.6% of slice). On a whole-heart analysis, T1 measurements of left ventricular mass, AAR, and myocardial salvage correlated to microsphere measures (R(2) = 0.94) with good agreement (mean ± 2 SD: -1.4 ± 11.2 g of myocardium). Corresponding T2 measurements of left ventricular mass, AAR, and salvage correlated to microsphere analysis (R(2) = 0.96; mean ± 2 SD: agreement 1.6 ± 9.2 g of myocardium). This yielded a median infarct size of 30% of the AAR (range 12% to 52% of AAR). CONCLUSIONS For determining AAR after acute myocardial infarction, noncontrast T1 mapping and T2 mapping sequences yield similar quantitative results, and both agree well with microspheres. The relaxation properties T1 and T2 both change in a way that is consistent with the presence of myocardial edema following myocardial ischemia/reperfusion.

Dynamic autocalibrated parallel imaging using temporal GRAPPA (TGRAPPA).

Current parallel imaging techniques for accelerated imaging require a fully encoded reference data set to estimate the spatial coil sensitivity information needed for reconstruction. In dynamic parallel imaging a time‐interleaved acquisition scheme can be used, which eliminates the need for separately acquiring additional reference data, since the signal from directly adjacent time frames can be merged to build a set of fully encoded full‐resolution reference data for coil calibration. In this work, we demonstrate that a time‐interleaved sampling scheme, in combination with autocalibrated GRAPPA (referred to as TGRAPPA), allows one to easily update the coil weights for the GRAPPA algorithm dynamically, thereby improving the acquisition efficiency. This method may update coil sensitivity estimates frame by frame, thereby tracking changes in relative coil sensitivities that may occur during the data acquisition. Magn Reson Med 53:981–985, 2005. Published 2005 Wiley‐Liss, Inc.

Extracellular volume fraction mapping in the myocardium, part 1: evaluation of an automated method

BackgroundDisturbances in the myocardial extracellular volume fraction (ECV), such as diffuse or focal myocardial fibrosis or edema, are hallmarks of heart disease. Diffuse ECV changes are difficult to assess or quantify with cardiovascular magnetic resonance (CMR) using conventional late gadolinium enhancement (LGE), or pre- or post-contrast T1-mapping alone. ECV measurement circumvents factors that confound T1-weighted images or T1-maps, and has been shown to correlate well with diffuse myocardial fibrosis. The goal of this study was to develop and evaluate an automated method for producing a pixel-wise map of ECV that would be adequately robust for clinical work flow.MethodsECV maps were automatically generated from T1-maps acquired pre- and post-contrast calibrated by blood hematocrit. The algorithm incorporates correction of respiratory motion that occurs due to insufficient breath-holding and due to misregistration between breath-holds, as well as automated identification of the blood pool. Images were visually scored on a 5-point scale from non-diagnostic (1) to excellent (5).ResultsThe quality score of ECV maps was 4.23 ± 0.83 (m ± SD), scored for n = 600 maps from 338 patients with 83% either excellent or good. Co-registration of the pre-and post-contrast images improved the image quality for ECV maps in 81% of the cases. ECV of normal myocardium was 25.4 ± 2.5% (m ± SD) using motion correction and co-registration values and was 31.5 ± 8.7% without motion correction and co-registration.ConclusionsFully automated motion correction and co-registration of breath-holds significantly improve the quality of ECV maps, thus making the generation of ECV-maps feasible for clinical work flow.