T1 MAPPING METHODOLOGY
A T1 map of the myocardium is a parametric reconstructed image,
where each pixel’s intensity directly corresponds to the T1 relaxation time of the corresponding myocardial voxel.
T1 mapping can be performed with high spatial resolution by using 1.5T or 3T magnetic resonance imaging scanners.
Different CMR acquisition sequences have been used to obtain myocardial T1 maps:
-MOLLI (Modified Look-Locker Inversion Recovery sequence)29
-VAST (Variable Sampling of the k-space in Time) inversion-recovery prepared 2D fast gradient echo sequence with variable sampling of k-space30
-ShMOLLI (Shortened Modified Look-Locker Inversion Recovery method)31: this method generates immediate,
high-resolution myocardial T1-maps in a short breath-hold with high precision.
Full recovery of the longitudinal magnetization between sequential inversion pulses is not achieved,
but conditional interpretation of samples for reconstruction of T1-maps is used to yield accurate measurements.
-Look-Locker sequence32
This is an essential point to consider before performing myocardial T1 maps,
because it directly influences the accuracy and reproducibility of the final T1 measurements.
This will also be considered when comparing results between different studies.
Different T1 mapping strategies will have varying sensitivities to motion artifacts,
heart rate,
and intrinsic T1 values ranges29.
The most assessed T1 mapping sequence has been described by Messroghli et al.6,29 and is the MOLLI sequence that provides high-resolution T1 maps of human myocardium in native and post-contrast situations within a single breath hold.
This sequence has been described,
optimized,
and tested in phantom studies,
on healthy volunteers,
and ischaemic cardiomyopathy patients.
Although it is sensitive to heart rate extreme values and tends to slightly underestimate the true T1 value,
the method allows a rapid and highly reproducible T1 map of heart with high levels of intra and inter-observer agreement33.
T1 MAPPING USING MOLLI: SEQUENCE DESCRIPTION
T1 mapping is performed using ECG triggered Look-Locker Inversion Recovery (MOLLI) 6,29.
MOLLI is a single-section T1 mapping technique that consists of three inversion-recovery prepared ECG-synchronized Look-Locker experiments (“trains”),
which are performed consecutively within one breath hold.
Each of the three trains starts with an inversion pulse that uses a specific inversion time (inversions with slightly shifted TI times within one protocol),
after which multiple single-shot images are acquired in consecutive heartbeats.
By combining the three inversions,
the relaxation curve is sampled in an interleaved manner,
resulting in a sufficient number of points for accurate T1 quantification.
All images are acquired with the same trigger delay time in end diastole Fig. 14.
To generate the inline T1 map,
the acquired inversion recovery images are first registered using a motion correction algorithm (MOCO) which is based on estimating synthetic images presenting contrast changes similar to the acquired images solving a variational energy minimization problem34.
Thereafter,
the T1 is computed on a per-pixel basis by performing a non-linear curve fitting using the three parameter signal model 34.
The groups of images results in a set of 11 source images (traditional MOLLI protocol),
which are identical except for their different effective inversion times (in inversion time order).
By merging these raw images into one data set,
T1 values can be computed for every pixel with three parameter curve fitting; a map of T1 in the imaging section can then be generated from these pixel values35 Fig. 15.
T1 maps can be obtained any time before or after gadolinium contrast administration.
Native T1 (noncontrast T1) distinguishes normal from abnormal myocardium,
reflecting myocardial disease involving the myocyte and interstitium.
The use of gadolinium based contrast agents allows a direct measurement of the size of the extracellular space,
reflecting interstitial disease.
We perform the T1 maps with a 3T system (Magneton TIM-Trio,
Siemens Healthcare,
Erlangen,
Germany) using a 32-chanel cardiac RF coil for signal reception,
the integrated body RF coil for transmission,
and ECG for cardiac gating.
Data are acquired in basal,
mid-ventricular and apical short axis planes and in 4 chamber plane.
Data are obtained in end-diastole using a cardiac gated,
SSFP-based Modified Look-Locker Inversion Recovery (MOLLI) technique29.
Imaging parameters are: TR=2.6-2.7 ms,
TE =1.0-1,1 ms,
FA = 35º,
FOV=(380x416) mm2,
matrix=256x165,
slice thickness=6 mm,
BW=1028 Hz/px,
GRAPPA acceleration factor 2,
linear phase-encoding ordering,
minimum TI of 129 ms.
To generate a pixel-wise myocardial T1 map,
single-shot SSFP images are acquired at different inversion times (pattern 3-2-3) and registered prior to a non-linear least-square curve fitting 6.
- T1 mapping-quantitative assessment
A region of interest (ROI) is placed on the basal septum in a 4-chamber view Fig. 16.
We ensure that the ROI is definitely within the myocardium and do not include blood or epicardial fat.
The resulting pixel by pixel color T1 maps are displayed using a customized table (0-2000 ms) where normal myocardium is purple and increasing T1 ranges from yellow to orange. Normal values of native T1 at 3T (Magneton TIM-Trio,
Siemens) with MOLLI sequence are 1031±24 ms.
NATIVE T1 MAP: SCIENTIFIC AND CLINICAL RELEVANCE
Native (noncontrast) T1 reflects myocardial disease involving the myocyte and interstitium.
Native T1 changes can detect pathologically important processes related to excess water in oedema36,
protein deposition37,
and other T1-altering substances such as lipid38 or iron39 (hemorrhage,
siderosis),
without the need for a gadolinium based contrast agent.
Alterations of myocardial native T1 can therefore signal both cardiac diseases (acute coronary syndromes ,
infarction,
myocarditis,
diffuse fibrosis causes (all high T1),
and systemic diseases such as cardiac amyloid Fig. 17 (high T1),
Anderson-Fabry disease (low T1) and siderosis (low T1).
When combined in a clinical scan protocol,
early evidence suggests that native T1 mapping can reveal pathology such as area at risk in acute coronary syndromes Fig. 18,
Fig. 19 ,
previously unsuspected pathologies (global myocarditis without LGE) and preclinical disease or unsuspected cardiac involvement (iron,
Fabry disease,
amyloid).
Bull et al.40 have shown the usefulness of native T1 maps in the detection of fibrosis in patients with aortic stenosis Fig. 20 .
T1 values correlate with percentage collagen volume fraction as measured from histology in patients with aortic stenosis Fig. 21 .
Native T1 values are increased in patients with aortic stenosis,
and native T1 values in aortic stenosis increase with lesion severity.
In addition native T1 need not exclude patients with severe renal dysfunction or pregnancy.
A problem with these techniques is that they measure a composite myocardial signal from both interstitium and myocytes.
EXTRACELLULAR VOLUME FRACTION : SCIENTIFIC AND CLINICAL RELEVANCE
The use of an extrinsic contrast agent adds another dimension to CMR tissue characterization.
The interstitial space can be assessed directly using standard gadolinium chelates.
These low-molecular weight,
purely extracellular agents are small enough to pass across the vascular wall into the extracellular space,
yet are large enough not to be able to penetrate cells with intact membranes.
They accumulate passively in the gaps between cells through post-bolus tracer kinetics and the increased ECV of interstitial expansion in “scar” tissue2.
This forms the basis of the LGE technique for detection of focal fibrosis such as seen in MI,
but recent developments have built upon this and allow scrutiny of diffuse interstitial expansion.
At a fixed time,
after contrast administration,
T1 may be reduced in cardiac disease suggesting increased myocardial interstitial space30.
The post-contrast T1 maps can be assessed at different time points after contrast administration and describe a curve of myocardial T1 recovery reflecting the contrast agent wash-out33 Fig. 22.
Post-contrast T1 values of scarred myocardium (replacement fibrosis) are significantly shorter than those of normal myocardium due to the retention of gadolinium contrast in fibrotic tissue41.
Iles et al.
demonstrated a significant correlation between histologic fibrosis and myocardial post-contrast T1 time in patients with heart failure30.
However,
care is needed as the disease may have altered body composition (a higher percentage of body fat and,
thus,
a greater contrast dose per unit of total body extra-cellular water),
reduced renal function,
or altered haematocrit.
If,
instead,
the ratio of signal change in blood and myocardium after contrast administration is calculated,
corrected by the haematocrit,
the (ECV,
which is the interstitial space,
can be calculated,
avoiding confounding factors such as heart rate,
body composition and renal clearance.
The ECV technique introduces a potentially important new method to examine the myocardium because it is sensitive to the distribution of the left ventricular myocardium into its cellular and extracellular interstitial (extracellular matrix [ECM]) compartments.
Alterations in these compartments occur from different physiologic and pathophysiologic biologic processes42.
The ECV of the myocardium reflects the volume fraction of heart tissue that is not taken by cells.
ECV maps can also be generated on a pixel-wise basis if native and post-contrast T1 images are coregistered,
quantified,
and adjusted for the haematocrit43 Fig. 23 .
Expansion of the myocardial ECV represents a nonspecific increase in free water in the myocardium and occurs in a variety of pathologies,
including focal and diffuse fibrosis,
oedema,
and amyloidosis.
In the absence of amyloid or oedema44,
expansion of the myocardial collagen volume fraction is responsible for most ECM expansion which culminates in mechanical,
electrical and vasomotor dysfunction.
Fibrosis is associated with a number of conditions and is considered to represent a final common pathway of myocardial disease from a variety of insults.
ECV MEASUREMENT
The ECV may be estimated from the concentration of extracellular contrast agent in the myocardium relative to the blood in a dynamic steady state.
The contrast agent distributes between cells embedded in the interstitium (extracellular space) and blood plasma such that the relative pre- and post-contrast signal changes measure the myocardial ECV.
- Theoretical background for ECV measurements
CMR can measure the fractional distribution volume of extracellular contrast agents and the ECV fraction of the myocardium2. T1 is a time constant describing the longitudinal relaxation rate,
and its reciprocal (1/T1) is referred to as R1.
The change in R1 (ΔR1) is defined as:
ΔR1=(R1post-contrast)–(R1pre-contrat) (1)
Where R1post-contrast is the R1 value of a tissue after the administration of a gadolinium based contrast agent,
and (R1pre-contrast) is the R1 value prior to contrast administration.
Importantly,
ΔR1 is proportional to contrast agent concentration:
ΔR1 = r1 [CA] (2)
Where r1 is a constant representing the T1-relaxitivity of the given contrast and [CA] is the concentration of that contrast agent.
If the ratio of the contrast agent concentration between two tissues is in equilibrium or in dynamic equilibrium,
then the contrast agent concentration ratio is equal to the ΔR1 ratio of these tissues since r1 is a constant which cancels out.
For myocardium and blood this may be expressed as:
ΔR1myo / ΔR1blood = [CA]myo / [CA]blood (3)
Where ΔR1myo is the ΔR1 for myocardium,
ΔR1blood is the ΔR1blood for the blood,
[CA]myo is the contrast agent concentration in the myocardium and [CA]blood is the contrast agent concentration in the blood.
Gadolinium (Gd) chelates,
such as Gd-DTPA,
are extracellular agents because they freely pass across the vascular wall into the extracellular space but are excluded from the intracellular space.
The ratio of contrast agent concentrations between myocardium and blood equals the ratio of extracellular volume between the tissues.
[CA]myo / [CA]blood = ECVmyo / ECVblood (4)
Where ECVmyo is the extracellular volume fraction of the myocardium and ECVblood is the ECV of the blood.
The ECV is defined as the fraction of a given tissue which is comprised of extracellular space (range 0-100%).
The ECV of the blood is defined as the fraction of the blood volume which is not composed of blood cells,
in other words,
the fraction composed of plasma.
The plasma volume fraction can be measured as one minus haematocrit.
ECVblood = [1-haematocrit] (5)
By combining equations [3],
[4] and [5] and solving for the ECV of the myocardium:
ECVmyo = [1-haematocrit] x ΔR1myo / ΔR1blood Fig. 24
The measurements are only valid for tissues where contrast agent concentration is in equilibrium (steady state) or dynamic equilibrium (dynamic steady state) with the contrast agent concentration in the blood pool.
Following an intravenous injection,
contrast agents are continuously cleared from the blood via renal clearance.
If the contrast exchange rate between the blood and the tissue of interest is faster than the renal clearance,
then the ratio of contrast agent concentration in the tissue and the blood will,
after the short initial equilibration period,
achieve a dynamic equilibrium and remain unchanged over time2.
- ECV measurement techniques using CMR
Myocardial ECV can be measured with T1 mapping before and after contrast agent if the contrast agent distribution between blood/myocardium is at equilibrium.
Equilibrium distribution can be achieved with a primed contrast infusion (equilibrium contrast-CMR [EQ-CMR]) or might be approximated by the dynamic equilibration achieved by delayed post-bolus measurement.
- Equilibrium contrast cardiovascular magnetic resonance (EQ-CMR)45
This is a robust,
noninvasive method to quantify diffuse myocardial fibrosis,
which have been validated against the current gold standard of surgical myocardial biopsy collagen volume fraction quantification in patients with aortic stenosis and hypertrophic cardiomyopathy.
This method is based in three elements:
- A bolus of the extracellular contrast agent gadolinium (Gd-DTPA) followed by a continuous infusion to achieve blood/myocardial contrast equilibrium
- A blood test to measure the ECV of the blood (1-haematocrit)
- CMR before and after contrast equilibrium to measure changes in tissue signal
This allows for the calculation of myocardial ECV which closely reflects the amount of fibrosis because collagen is aqueous and Gd-DTPA is an extracellular tracer that occupy this space freely.46
Contrast equilibrium is achieved by primed infusion (a loading bolus followed by a slow continuous infusion) with the following protocol45:
- T1 measurement sequence performed pre-contrast
- Bolus of Gd (0,1 mmol/kg)
- 15-minute pause
- Infusion of Gd at a rate of 0.0011 mmol/kg/min (equivalent to 0.1 mmol/kg over 90 minutes)
- At any time between 45 and 80 minutes after the bolus,
the patient is returned to the scanner and the T1 measurement repeated
The primed continuous infusion removes contrast kinetic effects,
measuring diffuse fibrosis in vivo.
With this technique the patient spends additional time in the department (30 to 90 minutes) during the continuous infusion,
but the flexibility in timing of the post-infusion scan means this can be incorporated into the clinical workflow.
ECV can be measured with simple Gd-DTPA contrast bolus as accurately as with an infusion,
but with slightly less precision47.
The bolus strategy to measure myocardial ECV simplifies the ECV data acquisition protocol and facilitates its integration into routine CMR practice.
At a sufficient time after a single contrast bolus,
a dynamic equilibrium exists47 –principally because contrast flux between tissue compartments is faster than renal excretion- allowing the equivalent ECV measurement.
This technique that provides short-term prognostic information28 has been validated histologically in distinct disease groups and the correlation with collagen volume fraction is similar to that with the infusion technique and do not differ statistically48.
The dynamic or “pseudo-equilibrium” technique is achieved with the following protocol Fig. 25:
- T1 measurement sequence performed pre-contrast
- Bolus of Gd (0.1 mmol/kg48 ,
0,15 mmol/kg51 or 0,2 mmol/kg47)
- 15-minute pause (dynamic equilibrium time)
- T1 measurements post-contrast
When compared with infusion-derived ECV (EQ-CMR),
the bolus only approach seems to be equivalent provided that the disease under study has an ECV below 0.448.
Above this (amyloid,
LGE areas of hypertrophic cardiomyopathy and chronic MI) the bolus only approach consistently and increasingly provides a higher ECV.
For infarction,
however,
contrast equilibration does not seem to be established in acute infarct zones when complicated by microvascular obstruction.
In chronic infarction,
there is evidence that equilibration can be reached after 20 minutes (with higher dose of contrast agent: 0,2 mmol/kg)52,53.
These findings are important,
because an ECV measurement with a bolus only technique is extremely easy to incorporate into routine clinical practice—a single breath-hold, of approximately 8 seconds,
before and after the contrast agent administration is all that is required (a total of 6 breath-holds for a 16-segment [“whole-heart”] approach).
Fig. 26 The approach might also be generalizable to other organs49 and computed tomography with iodinated contrast agents50.
The bolus only technique would be good enough to measure ECV across a range of cardiac diseases48.
MYOCARDIAL T1 AND ECV: REFERENCE VALUES
T1 values are affected by confounding variables such as field strength,
gadolinium contrast type and dose,
scanning time and the patient’s renal function.
Due to these factors,
T1 times cannot be readily compared to T1 data from other centers.
There are different T1 reference values in the literature depending on the field strength,
the scanner manufacturer,
the sequence and other parameters related with the acquisition protocol and the post-processing.
In order to use native myocardial T1-mapping to accurately identify disease states,
it is advisable to obtain the reference values in each scenario performing a study with healthy volunteers Fig. 27.
In contrast,
ECV is an inherent physiological property that should not be affected by these variables.
The ECV data of normal volunteers do not significantly differ between the different studies (24.1%47,
26.7%51).
This technique introduces a potentially new method to examine the myocardium.
NATIVE T1 MAPPING AND ECV: CMR BIOMARKERS
Native T1 mapping measures of myocardium permit noninvasive detection of biologically important processes which promise to improve diagnosis,
measures of disease severity,
and potentially prognosis.
Quantitative T1-mapping is rapidly becoming a clinical tool CMR to objectively distinguish normal from diseased myocardium.
Cardiac T1-mapping without the use of exogenous contrast agents has been shown to be sensitive to a variety of pathologies,
notably acute MI,
myocarditis and cardiac amyloidosis,
all of which demonstrate significant (i.e.
20-30%) increase in native T1 times,
as well as other pathologies that decreases T1 like Anderson-Fabry disease.
Although currently the study of diffuse fibrosis predominantly concentrates on post-contrast T1-mapping,
native T1-mapping holds significant promise in this field.
Native T1-mapping appears to be a highly reproducible,
robust and stable biomarker for characterizing the human myocardium.
Native myocardial T1 exhibit a narrow normal range with limited variability related to common technical and physiologic factors,
rendering it a potential method for quantitative disease detection without the need for exogenous contrast agents.
Early data indicate that ECV measures appear to be as prognostically important as LVEF56 which underscores the biologic importance of the interstitium.
This technique allows dichotomize between myocyte-ECM expansion.
Neither T1 mapping nor ECV directly measure the extracellular matrix.
Rather,
ECV measures the space the ECM occupies which is a useful surrogate.
ECV has robust histological validation as an ECM measurement which correlates with the collagen volume fraction45,57,58.
This advance is important because myocardial fibrosis is ubiquitous and associated with myocardial remodeling.
In the absence of amyloidosis,
other forms of infiltrative disease,
or clinical conditions that would create myocardial oedema,
and acknowledging the other components of ECM59,
ECV is a CMR biomarker for myocardial fibrosis.
CLINICAL APPLICATIONS OF INTERSTITIAL IMAGING
The non-invasive assessment of interstitial expansion may find a variety of clinical uses.
Fibrosis may be an early phenomenon in some diseases such as hypertrophic cardiomyopathy60.
Carriers of the mutation may have increased diffuse myocardial fibrosis without showing any other phenotypic trait of the disease.
This fibrosis has a considerable effect on the heart before the onset of hypertrophy.
Therefore these techniques can help to identify people at risk of arrhythmias,
heart failure and sudden death.
Furthermore,
the development of therapies to mitigate fibrosis can change the natural course of this disease.
In established disease,
fibrosis-modulating therapies (eg,
the renin-angiotensin antagonists and spironolactone) are established in heart failure but have not been well explored in other conditions such as cardiomyopathy and congenital heart disease.
T1 mapping and ECV quantificatin may guide and monitor treatment and predict outcome in these diseases.
Interstitial measurement may sub-type diseases such as hypertension or hypertrophic cardiomyopathy to permit individualization of treatment through targeted anti-fibrotic therapy.
Fibrosis may also be linked to arrhythmia outcomes raising the possibility of using these techniques to target device therapy.
1. AFTERLOAD STATES (AORTIC STENOSIS AND HYPERTENSION)
The range of diffuse fibrosis on biopsy in aortic stenosis patients is wide: 6% to 40% of total myocardium45 Fig. 21 .
In this condition,
as in other diseases,
evidence suggests that the extent of fibrosis is an important determinant of outcome and may explain why valve stenosis severity and hemodynamic parameters alone only partially explain symptoms and outcome.
Burden of myocardial fibrosis in severe aortic stenosis has a negative impact on postoperative outcome62 and so a method of preoperative quantification is important.
Histological validation of non-contrast T1 mapping40 Fig. 20 and EQ-CMR technique exists in this pathology45.
Diffuse fibrosis is an important clinical parameter and is associated with worsening ventricular systolic and diastolic function and adverse remodeling.
More extensive fibrosis is associated with advanced heart failure,
regardless of its cause.
It is also a potentially reversible phenomenon,
and several therapies seem to exert their beneficial effects via myocardial fibrosis regulation61
2. HYPERTROPHIC CARDIOMYOPATHY
Limited early histological validation of CMR techniques exist in hypertrophic cardiomyopathy 45.
The correlation in aortic stenosis is stronger than that found in hypertrophic cardiomyopathy45,
because fibrosis in the last condition is thought to be less diffuse in nature than in aortic stenosis Fig. 28,
Fig. 29 .
Myectomy samples show a more patchy distribution of fibrosis in hypertrophic cardiomyopathy45.
3. DILATED CARDIOMYOPATHY
There are some preliminary studies indicating that interstitial expansion and therefore diffuse myocardial fibrosis have an inverse correlation with ejection fraction in famial dilated cardiomyopathy.
CMR T1 mapping and ECV quantification can reliably and non-invasively measure increases in diffuse myocardial fibrosis even in mild famial dilated cardiomyopathies63 Fig. 30,
Fig. 31,
Fig. 32.
4. AMYLOIDOSIS
Amyloidosis is a group of diseases in which proteins misfold to form insoluble fibrils that accumulate in the extracellular space and disrupt the structure and function of many tissues and organs64.
Amyloid diseases are caused by as many as 23 different pre-cursor proteins already described.
Cardiologists predominantly encounter three main types of amyloidosis that affect the heart65: light chain (AL) amyloidosis,
senile systemic amyloidosis (SSA) and hereditary amyloidosis,
most commonly caused by a mutant form of transthyretin Fig. 33 .
In the third world,
secondary amyloid (AA) is more prevalent,
due to chronic infections and inadequately treated inflammatory conditions.
Systemic AL amyloidosis is caused by the accumulation of amyloid deposits derived from monoclonal immunoglobulin light chains in the interstitium of organs throughout the body.
It is the most common and serious type of amyloidosis,
with treatment comprising chemotherapy directed at the underling plasma cell dyscrasia.
Cardiac involvement is frequent,
a principal driver of prognosis,
and may be the presenting feature of the disease66.
In hereditary amyloidosis,
cardiac involvement can limit short-term and long-term results of orthotopic liver transplantation67 and influence decisions to perform combined heart-liver transplantation.
Although endomyocardial biopsy is the gold standard for demonstrating cardiac amyloid deposits,
it is not routinely performed because it is invasive and,
in practice,
much reliance has been placed on the collective diagnostic value of clinical features,
electrocardiography and echocardiography,
supported by the presence of amyloid in extracardiac sites64.
Evaluation of early stage cardiac involvement can be challenging.
Confounding features are often present66,
commonly including left ventricular hypertrophy and abnormal diastolic function associated with renal failure,
diabetes mellitus,
or hypertension.
Definitive diagnosis of cardiac amyloidosis,
which has critical implications for choice of treatment,
generally requires cardiac biopsy which is invasive and prone to sampling error.
The extracellular deposition of amyloid fibrils can be massive (amyloid may constitute most of the mass of the heart),
producing a change in the intrinsic T1 signal. CMR with LGE provides unique information on myocardial tissue characterization in patients with cardiac amyloidosis68.
A characteristic appearance of global,
subendocardial LGE Fig. 34 is the hallmark for identifying cardiac involvement,
which substantially aids the noninvasive diagnosis of cardiac amyloid,
and correlates with prognosis69.
However,
the LGE technique has limitations in evaluating patients with suspected cardiac amyloidosis,
many of whom have significant renal impairment making administration of a gadolinium-based contrast problematic.
Furthermore,
the pattern of LGE may be atypical and patchy Fig. 35 ,
even in patients with life-threatening disease.
Therefore,
a reproducible,
CMR technique that can provide accurate identification of cardiac amyloidosis and,
quantitative assessment of myocardial amyloid load is of great value.
The early diagnosis of cardiac involvement can be challenging.
Patients with systemic AL amyloidosis show markedly increased noncontrast T1 relaxation times in the myocardium.
The T1 times are also increased in many patients in whom currently used clinical investigations suggest cardiac involvement is uncertain or absent Fig. 36.
Noncontrast T1 mapping,
and CMR (EQ-CMR) technique that measures the myocardial ECV fraction,
are effective methods for noninvasively quantifying cardiac amyloid burden providing diagnostic information in patients with suspected cardiac amyloidosis.
Noncontrast T1 mapping has high diagnostic accuracy for detecting cardiac amyloidosis,
correlates well with markers of systolic and diastolic dysfunction,
and is potentially more sensitive for detecting early disease than LGE imaging70.
Among amyloid patients with overt cardiac involvement,
the increasing T1 values are more pronounced than in patients with aortic stenosis and a similar degree of ventricular wall thickening.
Elevated myocardial T1 likely reflects the severity of cardiac involvement and may represent a direct marker of cardiac amyloid load70.
Expansion of the myocardial ECV in amyloidosis is higher than in any other disease,
generating diagnostic specificity above a certain threshold Fig. 37,
Fig. 38 .
For example,
in the series of Banypersad44 the average ECV value for definite cardiac AL amyloid was 0.488 with the lowest value being 0.423.
ECV correlates with cardiac parameters by echocardiography and conventional cardiovascular magnetic resonance (eg,
indexed left ventricular mass).
There are also significant correlations with N-terminal pro-brain natriuretic peptid and Troponin T.
ECV is associated with smaller QRS voltages and correlates with poorer performance in the 6-minute walk test44.
Myocardial ECV measurement has potential to become the first noninvasive test to quantify cardiac amyloid burden.
5. ACUTE MYICARDIAL INJURY: MYOCARDITIS AND MYOCARDIAL INFARCTION
Acute myocardial injury is accompanied by intracellular and interstitial oedema and is traditionally detected by increased T2 signal at T2-weighted CMR,
although T2 Fig. 39 and native T1 Fig. 40 mapping may prove to be equally effective and robust36.
In severe cases,
cellular necrosis and subsequent fibrosis are delineated by LGE Fig. 41,
again confirming expansion,
but also hypoperfusion.
A differential in expansion,
or ECV,
has been demonstrated between the salvaged area at risk,
the infarct zone and the remote myocardium in acute myocardial infarction71 Fig. 18 Fig. 19 .
In the longer term,
a negative correlation is seen between increasing ECV of remote myocardium and lower ejection fraction72.
T1 mapping techniques for quantifying diffuse interstitial expansion in myocarditis have yet to be explored.
6. ANDERSON FABRY DISEASE
Anderson Fabry disease is a rare but under-diagnosed intracellular lipid disorder which can cause left ventricular hypertrophy.
Anderson-Fabry disease is an X-linked storage disease characterized by multi-organ involvement and premature death due to cardiac failure,
arrhythmia,
stroke and renal failure.
The disease is caused by a deficiency in the enzyme alpha-galactosidase A which results in the accumulation of glycosphingolipids within lysosomes and,
in some tissues,
progressive fibrosis73.
As treatment with recombinant enzyme has been shown to reverse or slow disease progression when initiated before reversible end-organ damage has occurred,
early detection of glycosphingolipids deposition is imperative74.
At present this can only be achieved in the heart by performing endomyocardial biopsy which has several limitations including the risk of myocardial perforation and sampling error75.
Left ventricular hypertrophy is a late manifestation in this disease,
typically appearing after the third decade in men and the fourth in women,
and correlates poorly with myocardial glycophingolipid content76.
As fat is known to possess a very low T1,
left ventricular myocardial non-contrast T1 can be used as a surrogate marker to detect myocardial glycosphingolipid storage before the development of left ventricular hypertrophy has occurred77. Furthermore,
in patients with established left ventricular hypertrophy,
the T1 allows Anderson Fabry disease to be differentiated from other more common causes of left ventricular hypertrophy due to the presence glycosphingolipids in this condition.
On the other hand,
in this disease are commonly found foci of fibrosis in the inferolateral wall and therefore enhanced areas in the sequence of LGE at this location Fig. 42 .