**Author details**

Kazumasu Sasaki1,2\*, Tatsushi Mutoh3,4, Kinji Shirota5 and Ryuta Kawashima6

\*Address all correspondence to: kazumasu.sasaki.d8@tohoku.ac.jp

1 Department of Functional Brain Imaging and Preclinical Evaluation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan

2 Sendai Animal Care and Research Center, Sendai, Japan

3 Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan

4 Department of Surgical Neurology, Research Institute for Brain and Blood Vessels‐AKITA, Akita, Japan

5 Department of Veterinary Pathology, School of Veterinary Medicine, Azabu University, Ka‐ nagawa, Japan

6 Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, To‐ hoku University, Sendai, Japan

### **References**

[1] Sirasaka T, Miyagawa S, Fukushima S, et al. Skeletal myoblast cell sheet implantation ameliorates both systolic and diastolic cardiac performance in canine dilated cardio‐ myopathy model. *Transplantation.* 2016;100:295–302.


[17] Tidholm A, Häggstrüm J, Borgarelli M, et al. Canine idiopathic dilated cardiomyopathy. Part I: aetiology, clinical characteristics, epidemiology and pathology. *Vet J.* 2001;162:92– 107.

[2] Lacroix D, Gluais P, Marquié C, et al. Repolarization abnormalities and their arrhyth‐ mogenic consequences in porcine tachycardia‐induced cardiomyopathy. *Cardiovasc*

[3] Mittal A, Sharma R, Prasad R, et al. Role of cardiac TBX20 in dilated cardiomyopathy.

[4] Wilder T, Ryba DM, Wieczorek DF, et al. N‐acetylcysteine *reverses* diastolic dysfunction and hypertrophy in familial hypertrophic cardiomyopathy. *Am J Physiol Heart Circ*

[5] Frey N, Franz WM, Gloeckner K, et al. Transgenic rat hearts expressing a human cardiac troponin T deletion reveal diastolic dysfunction and ventricular arrhythmias. *Cardio‐*

[6] Sanbe A, James J, Tuzcu V, et al. Transgenic rabbit model for human troponin I‐based

[7] Geens JH, Trenson S, Rega FR, et al. Ovine models for chronic heart failure. *Int J Artif*

[8] Tidholm A, Jünsson L. Histologic characterization of canine dilated cardiomyopathy

[9] Martin MW, Stafford Johnson MJ, Strehlau G, et al. Canine *dilated* cardiomyopathy: a retrospective study of prognostic findings in 367 clinical cases. *J Small Anim Pract.*

[10] Christiansen LB, Prats C, Hyttel P, Koch J. Ultrastructural myocardial changes in seven cats with spontaneous hypertrophic cardiomyopathy. *J Vet Cardiol.* 2015;17: 220–232.

[11] Maron BJ, Fox PR. Hypertrophic cardiomyopathy in man and cats. *J Vet Cardiol.*

[12] Ferasin L. Feline myocardial disease *2: diagnosis*, prognosis and clinical management.

[13] Simpson S, Edwards J, Ferguson‐Mignan TF, et al. Genetics of human and canine dilated

[14] Kitteleson MD, Meurs KM, Harris SP. The genetic basis of hypertrophic cardiomyop‐

[15] Nelson RW, Couto CG., editors. Small animal internal medicine. St. Louis, MO: Elsevier

[16] Tilley LP, Smith, Jr FWK, Oyama MA, Sleeper MM. Manual of canine and feline

hypertrophic cardiomyopathy. *Circulation.* 2005;111:2330–2338.

*Res.* 2002;54:42–50.

340 Cardiomyopathies - Types and Treatments

*Mol Cell Biochem.* 2016;414:129–36.

*Physiol.* 2015;309:1720–1730.

*vascular Res.* 2000;47:254–264.

*Organs.* 2009;32:496–506.

*Vet Pathol.* 2005;42:1–8.

*J Feline Med Surg.* 2009;11:183–194.

cardiomyopathy. *Int J Genomics.* 2015;2015:204823.

athy in cats and humans. *J Vet Cardiol.* 2015;17:53–73.

cardiology. St. Louis, MO: Saunders Elsevier; 2008.

2010;51:428–436.

2015;17:6–9.

Mosby; 2014.


[46] Furuoka H, Yagi S, Murakami A, et al. Hereditary dilated cardiomyopathy in Holstein‐ Friesian cattle in Japan: association with hereditary myopathy of the diaphragmatic muscles. *J Comp Pathol.* 2001;125:159–165.

[31] Janus I, Noszczyk‐Nowak A, Nowak M, et al. A comparison of the histopathologic pattern of the left atrium in canine dilated cardiomyopathy and chronic mitral valve

[32] Tidholm A, Häggstrüm J, Jünsson L. Detection of attenuated wavy fibers in the myocardium of Newfoundlands without clinical or echocardiographic evidence of

[33] Tidholm A, Häggstrüm J, Jünsson L. Prevalence of attenuated wavy fibers in myocar‐ dium of dogs with dilated cardiomyopathy. *J Am Vet Med Assoc*. 1998;212:1732–1734.

[34] Harpster N. Boxer cardiomyopathy. *Vet Clin North Am Small Anim Pract*. 1991;21:989–

[35] Granstrüm S, Godiksen MT, Christiansen M, et al. Prevalence of hypertrophic cardio‐ myopathy in a cohort of British Shorthair cats in Denmark. *J Vet Intern Med.*

[36] Gundler S, Tidholm A, Häggstrüm J. Prevalence of myocardial hypertrophy in a population of asymptomatic Swedish Maine coon cats. *Acta Vet Scand*. 2008;50:22.

[37] Cesta MF, Baty CJ, Keene BW, et al. Pathology of end‐stage remodeling in a family of

[38] Saito Y, Suzuki Y, Kondo N, et al. Direct epicardial assist device using artificial rubber muscle in a swine model of pediatric dilated cardiomyopathy. *Int J Artif Organs.*

[39] Lin JH, Huang SY, Lee WC, et al. Echocardiographic features of pigs with spontaneous

[40] Collins DE, Eaton KA, Hoenerhoff MJ. Spontaneous dilated cardiomyopathy and right‐ sided heart failure as a differential diagnosis for hepatosis dietetica in a production pig.

[41] Shyu JJ, Cheng CH, Erlandson RA, et al. Ultrastructure of intramural coronary arteries in pigs with hypertrophic cardiomyopathy. *Cardiovasc Pathol.* 2000;11:104–111.

[42] Liu SK, Chiu YT, Shyu JJ, et al. Hypertrophic cardiomyopathy in pigs: quantitative

[43] Horiuchi N, Kumagai D, Matsumoto K, et al. Detection of the nonsense mutation of OPA3 gene in Holstein Friesian cattle with dilated cardiomyopathy in Japan. *J Vet Med*

[44] Van Vleet JF, Ferrans VJ. Myocardial diseases of animals. *Am J Pathol.* 1986;124:98–178.

[45] Owczarek‐Lipska M, Plattet P, Zipperle L, et al. A nonsense mutation in the optic atrophy 3 gene (OPA3) causes dilated cardiomyopathy in Red Holstein cattle. *Genomics.*

cats with hypertrophic cardiomyopathy. *Vet Pathol.* 2005;42:458–467.

hypertrophic cardiomyopathy. *Comp Med.* 2002;52:238–242.

pathologic features in 55 cases. *Cardiovasc Pathol.* 1994;3:261–268.

disease. *BMC Vet Res*. 2016;12:3.

342 Cardiomyopathies - Types and Treatments

1004.

2011;25:866–871.

2015;38:588–594.

*Comp Med.* 2015;65:327–332.

*Sci.* 2015;77:1281–1283.

2011;97:51–57.

heart disease. *Am J Vet Res*. 2000;61:238–241.


**Diagnosis and Invasive Treatments**

[61] Tidholm A, Jünsson L. Dilated cardiomyopathy in the Newfoundland: a study of 37

[62] Calvert CA, Pickus CW, Jacobs GJ, et al. Signalment, survival and prognostic factors in Doberman Pinschers with end‐stage cardiomyopathy. *J Vet Intern Med*. 1997;11:323–326.

[63] Everett RM, McGann J, Wimberly HC, et al. Dilated cardiomyopathy of Doberman Pinschers: retrospective histomorphologic evaluation of heart from 32 cases. *Vet*

[64] Vollmar AC, Fox PR, Meurs KM, et al. Dilated cardiomyopathy in juvenile Doberman

[65] Lobo L, Carvalheira J, Canada N, et al. Histologic characterization of dilated cardio‐

[66] Tilley LP, Liu S‐K. Cardiomyopathy in the dog. *Recent Adv Stud Cardiac Struct Metab*.

[67] Sandusky GE, Capen CC, Kerr KM. Histological and ultrastructural evaluation of cardiac lesions in idiopathic cardiomyopathy in dogs. *Can J Comp Med*. 1984;48:81–86.

[68] Alroy J, Rush JE, Freeman L, et al. Inherited infantile dilated cardiomyopathy in dogs: genetic, clinical, biochemical, and morphologic findings. *Am J of Med Genet*.

[69] Vollmar AC, Fox PR, Meurs KM, et al. Dilated cardiomyopathy in juvenile Doberman

myopathy in Estrela mountain dogs. *Vet Pathol.* 2010;47:637–642.

cases (1983–1994). *J Am Anim Hosp Assoc.* 1996;32:465–470.

*Pathol*. 1999;36:221–227.

344 Cardiomyopathies - Types and Treatments

1975;10:641–653.

2000;95:57–66.

Pinscher dogs. *J Vet Cardiol.* 2005;5:23–27.

Pinscher dogs. *J Vet Cardiol*. 2005;5:23–27.

#### **Cardiac Magnetic Resonance T1 Mapping in Cardiomyopathies Cardiac Magnetic Resonance T1 Mapping in Cardiomyopathies**

Christian R. Hamilton-Craig, Mark W. Strudwick and Christian R. Hamilton-Craig, Mark W. Strudwick and Graham J. Galloway

Graham J. Galloway

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/65327

#### **Abstract**

Cardiac magnetic resonance (CMR) imaging has been widely used to assess myocardial perfusion and scar and is the noninvasive reference standard for identification of focal myocardial fibrosis. However, the late gadolinium enhancement (LGE) technique is limited in its accuracy for absolute quantification and assessment of diffuse myocardial fibrosis by technical and pathophysiological features. CMR relaxometry, incorporating T1 mapping, has emerged as an accurate, reproducible, highly sensitive, and quantita‐ tive technique for the assessment of diffuse myocardial fibrosis in a number of disease states. We comprehensively review the physics behind CMR relaxometry, the evidence base, and the clinical applications of this emerging technique.

**Keywords:** cardiac magnetic resonance, T1 mapping, myocardial fibrosis, cardiomy‐ opathy

### **1. Introduction**

Cardiac Magnetic Resonance (CMR) imaging has been used widely to assess myocardial perfusion and scar [1–5]. It is the noninvasive reference standard for left and right ventricu‐ lar quantitation, as well as the assessment and quantitation of focal myocardial fibrosis (after infarction or due to other causes of cellular injury). Myocardial necrosis causes high signal on late gadolinium enhancement (LGE) inversion recovery T1‐weighted images with excellent signal‐noise ratios, and this has become the reference standard for noninvasive scar imaging in cardiomyopathies of various causes [1–4]. However, LGE is limited in its ability to assess and quantitate diffuse (nonfocal) myocardial injury and fibrosis. LGE is

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

affected by inconsistencies in acquisition parameters, such as choice inversion time, and in postprocessing when signal intensity thresholds may be arbitrarily applied to distinguish normal myocardium from fibrotic tissue [6, 7]. Moreover, the critical issue with LGE is that signal intensity is expressed on an arbitrary scale (*relative* signal intensity compared with "nulled" normal myocardium). Detection of myocardial fibrosis using *relative* differences between scar and normal myocardium tissue is therefore *qualitative*. Thus, in nonischemic cardiomyopathies, such as hypertension or diabetes, LGE CMR is unable to detect signal differential where the collagen deposition is diffuse and widespread throughout the myo‐ cardium [8].

### **2. CMR relaxometry**

CMR is an evolving technique, providing valuable and comprehensive data on the anatomy and functional integrity of both the heart and coronary blood vessels. Currently, CMR is performed at magnetic field strengths of 1.5 or 3 T.

### **3. T1 mapping with Look–Locker**

The initial technique to measure spin–lattice T1 relaxation time values was the eponymously named "Look–Locker" sequence (also known as "TI scout"). It has been widely used to estimate the optimal inversion time for assessment of myocardial LGE [9, 10]. It was originally proposed by Look and Locker in 1968 and analyzed more fully in 1970 [11] and consists of an initial inversion pulse, followed by a train of pulses with a constant, limited flip angle (7–15°).

The development of LL technique is summarized in **Table 1**.

The LL sequence has been widely applied in CMR due to its fast acquisition with minimal breath‐hold requirements. The LL sequence has been used to measure T1 values in patients with myocardial fibrosis [9]. However, it suffers from significant limitations: low flip angle RF pulse exciting the magnetization and the two RR intervals in the LL sequence are not sufficient for the magnetization to return to equilibrium. This causes *underestimation* of true T1 values using LL. Furthermore, the LL T1 images with different TIs are acquired at different cardiac phases. Therefore, images are "cine" with cardiac motion effect, which requires tedious manual tracking of the myocardial borders for each phase, a labour‐intensive and error‐prone process, which is challenging in clinical practice. The drawing of regions of interest "ROI" in myocardial segments requires adjusting for cardiac motion, which results in including blood pool (partial volume averaging) and artificially increasing the measured T1 [12].

To address these shortcomings, several myocardial T1 mapping sequences have been created, including modified Look‐Locker inversion (MOLLI) recovery.


**Table 1.** Summary of development of Look–Locker technique.

affected by inconsistencies in acquisition parameters, such as choice inversion time, and in postprocessing when signal intensity thresholds may be arbitrarily applied to distinguish normal myocardium from fibrotic tissue [6, 7]. Moreover, the critical issue with LGE is that signal intensity is expressed on an arbitrary scale (*relative* signal intensity compared with "nulled" normal myocardium). Detection of myocardial fibrosis using *relative* differences between scar and normal myocardium tissue is therefore *qualitative*. Thus, in nonischemic cardiomyopathies, such as hypertension or diabetes, LGE CMR is unable to detect signal differential where the collagen deposition is diffuse and widespread throughout the myo‐

CMR is an evolving technique, providing valuable and comprehensive data on the anatomy and functional integrity of both the heart and coronary blood vessels. Currently, CMR is

The initial technique to measure spin–lattice T1 relaxation time values was the eponymously named "Look–Locker" sequence (also known as "TI scout"). It has been widely used to estimate the optimal inversion time for assessment of myocardial LGE [9, 10]. It was originally proposed by Look and Locker in 1968 and analyzed more fully in 1970 [11] and consists of an initial inversion pulse, followed by a train of pulses with a constant, limited flip angle (7–15°).

The LL sequence has been widely applied in CMR due to its fast acquisition with minimal breath‐hold requirements. The LL sequence has been used to measure T1 values in patients with myocardial fibrosis [9]. However, it suffers from significant limitations: low flip angle RF pulse exciting the magnetization and the two RR intervals in the LL sequence are not sufficient for the magnetization to return to equilibrium. This causes *underestimation* of true T1 values using LL. Furthermore, the LL T1 images with different TIs are acquired at different cardiac phases. Therefore, images are "cine" with cardiac motion effect, which requires tedious manual tracking of the myocardial borders for each phase, a labour‐intensive and error‐prone process, which is challenging in clinical practice. The drawing of regions of interest "ROI" in myocardial segments requires adjusting for cardiac motion, which results in including blood pool (partial

To address these shortcomings, several myocardial T1 mapping sequences have been created,

cardium [8].

**2. CMR relaxometry**

348 Cardiomyopathies - Types and Treatments

performed at magnetic field strengths of 1.5 or 3 T.

The development of LL technique is summarized in **Table 1**.

volume averaging) and artificially increasing the measured T1 [12].

including modified Look‐Locker inversion (MOLLI) recovery.

**3. T1 mapping with Look–Locker**
