Academic literature on the topic 'Late gadolinium magnetic resonance imaging'

Purpose: To evaluate the utility of cardiac magnetic resonance T1 mapping in early systemic sclerosis and its association with skin score. Methods: In total, 24 consecutive patients with early systemic sclerosis referred for cardiovascular evaluation and 12 controls without systemic sclerosis were evaluated. All patients underwent cine, T1 mapping, and late gadolinium–enhanced cardiac magnetic resonance imaging. T1 mapping indices were compared between systemic sclerosis patients and controls (extracellular volume fraction, gadolinium partition coefficient (λ), pre-contrast T1, and post-contrast T1). The association between T1 mapping parameters and the modified Rodnan skin score was determined. Results: There were no significant differences in cardiac structure/function between systemic sclerosis patients and controls on cine imaging, and 8 of 24 (33%) systemic sclerosis patients had evidence of late gadolinium–enhanced cardiac magnetic resonance imaging (i.e. focal myocardial fibrosis). Of the T1 mapping parameters (indices indicative of diffuse myocardial fibrosis), extracellular volume fraction differentiated systemic sclerosis patients from controls the best, followed by λ, even when the eight systemic sclerosis patients with late gadolinium–enhanced cardiac magnetic resonance imaging were excluded. Extracellular volume fraction had a sensitivity and specificity of 75% and 75% for diffuse myocardial fibrosis (optimal abnormal cutoff value of >27% (area under receiver operating characteristic curve = 0.85)). In the 16 patients without evidence of late gadolinium–enhanced cardiac magnetic resonance imaging, each of the four cardiac magnetic resonance T1 mapping parameters (extracellular volume fraction, λ, Pre-T1 and Post-T1) correlated with modified Rodnan skin score ( R = 0.51–0.65, p = 0.007–0.043), indicating a correlation between systemic sclerosis cardiac and skin fibrosis. Conclusion: The four T1 mapping indices are significantly correlated with modified Rodnan skin score in patients with early systemic sclerosis. Quantification of diffuse myocardial fibrosis using extracellular volume fraction should be considered as a marker for cardiac involvement in systemic sclerosis clinical studies.

Cardiovascular magnetic resonance imaging (CMR) is a comprehensive and versatile diagnostic and prognostic imaging modality that plays an increasingly important role in management of patients with cardiovascular disease. In this review, we discuss CMR applications in nonischemic cardiomyopathy, ischemic heart disease, arrhythmias, right ventricular diseases, and valvular heart disease. We emphasize the quantitative nature of CMR in current practice, from volumes, function, myocardial strain analysis, and late gadolinium enhancement to parametric mapping, including T1, T2, and T2* relaxation times and extracellular volume fraction assessment.

Cardiovascular magnetic resonance imaging (MRI) has evolved over the last few years into a valuable tool for the diagnosis and management of cardiovascular diseases. Late gadolinium-enhanced MRI and stress myocardial perfusion MRI have been shown to be useful in detecting infarct tissue and in predicting myocardial viability and patient prognosis. The strengths of MRI lie in its ability to comprehensively image cardiac anatomy, function, perfusion, viability and physiology in ‘one-stop testing’ and to provide high-quality diagnostic information without the need for radiation. This article summarises the current clinical applications of MRI in interventional cardiology.

Abstract Given the higher amount of detail it offers, the use of magnetic resonance (MR) in the field of cardiology has increased, thus leading to a decrease in the use of invasive and irradiating methods for diagnosing various cardiovascular disorders. The only precautions for MR imaging are metallic implants and advanced-stage chronic kidney disease. For the acquisition of clear and dynamic myocardial images, methods such as spin echo imaging for anatomical description, steady-state free precession imaging for the assessment of ventricular cavity size and function, flow velocity encoding for blood flow measurements, radiofrequency tagging for dynamics, and even spectroscopy for metabolism evaluation are used. Cardiac magnetic resonance (CMR) is considered the gold standard imaging method for the anatomical characterization of the heart and obtaining information related to myocardial dynamics. In case of ischemic events, CMR is used for a detailed description of the necrotic area and the complications, and for tracking the ventricular remodeling. By administrating a contrast agent (gadolinium), the difference between sub-endothelial and transmural infarctions can be distinguished, highlighting even microvascular lesions responsible for the extension of the necrosis. The assessment of the dynamics of ventricular remodeling and viability through late gadolinium enhancement (LGE) technology highlights the area of fibrosis and the occurrence of late complications.

AbstractDanon disease is a rare entity associated with the clinical triad of mental retardation, skeletal myopathy, and severe hypertrophic cardiomyopathy. We report two cases of Danon disease and describe the results of the cardiac magnetic resonance imaging studies that were conducted to assess the pattern of cardiac hypertrophy.

Background: Cardiomyopathies are an important and heterogeneous group of diseases of the heart muscle in which tissue characterization has been extensively studied only ex-vivo so far. Cardiac magnetic resonance (CMR) can provide in vivo the detection of post-contrast deposition (so called Late Gadolinium Enhancement, LGE). The role of LGE in the differential diagnosis of cardiac diseases has advanced through the years, in particular thanks to its capability to differentiate post-ischemic scar (with subendocardial or transmural coronary artery-related deposition) versus non-ischemic scar of different aetiologies. Among cardiomyopathies, the prognostic significance of LGE pattern is not well established, with the exception of hypertrophic cardiomyopathy. Detection in vivo of LGE in different cardiomyopathies has been used as a surrogate of fibrosis, even if the real basis of contrast deposition is not well understood. To this regard, dilated cardiomyopathy (DCM) is characterized by diffuse interstitial fibrosis with or without replacement-type fibrosis, which are associated with worse prognosis. Another myocardial disease in which CMR offers the capability of a non-invasive tissue characterization is Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), an inherited heart muscle disease with progressive loss of myocardium and replacement by fibrofatty tissue. The extensively application of CMR to these cardiomyopathies and its comparison with traditional invasive and non-invasive techniques for diagnostic and prognostic purposes has been limited so far. Aim: in order to assess the clinical significance of LGE in DCM and ARVC, the following lines were pursued: 1) in patients with DCM the diagnostic and the prognostic value of LGE, in particular evaluating the possible different significance of various LGE patterns, total amount of LGE against survival, heart failure and ventricular arrhythmias; 2) in patients with ARVC the comparison between CMR findings and: 1a) traditional electrocardiographic features; 1b) scar detction by endocardial voltage mapping (EVM), and 1c) the prognostic significance of LGE; 3) the significance of CMR tissue abnormalities by comparing LGE and specimen heart and/or endomyocardial biopsy (EMB) findings in DCM and ARVC. Material and Methods: Between January 2007 and December 2010 we prospectively evaluated two different groups of patients referred to our Tertiary Referral Centre for a complete invasive and non-invasive evaluation for unexplained left ventricle (LV) dilatation (DCM Group, A) and for suspected ARVC (ARVC Group, B). DCM Group (A): we prospectively evaluated 210 patients referred for unexplained LV dilatation with subacute-chronic onset (≥ 1 month), with or without previous history of heart failure, who underwent during the same hospitalization to a complete screening including CMR with LGE, angiography and EMB. ARVC group (B): we prospectively evaluated 52 patients who were referred to our Tertiary Centre for susptected ARVC and in which the diagnosis was reached according to 1994 Task Force Criteria and 2010 Modified Criteria. Data on clinical history, ECG, ECG Holter monitoring, echocardiography, CMR and EMB in selected cases were collected. In a subgroup of patients an electrophysiological study with EVM was performed. For each subject enrolled, a clinical, ECG and echocardiographic follow-up was obtained. Results: Group A. On the basis of coronary angiography, patients were divided into two groups: ischemic (99 patients) and DCM (111 patients). Ischemic group patients were then excluded from the analysis. Compared to angiography, CMR showed an excellent accuracy (96.5%) for the identification of non-ischemic versus ischemic aetiology for LV dilatation. In the DCM group (111 patients) LGE was present (with a non-ischemic pattern) in 67 cases (60.4%) and absent in 44 (39.6%); no differences between RV and LV volumes and ejection fraction (EF) were found between the two groups. Out of 67 patients with positive LGE, a “gray” pattern was present in 12 patients (17.9%), a midwall/subepicardial stria in 49 (73.1%), a septal junction pattern (anterior and/or posterior) either isolated in 4 (5.9%) or associated with other patterns in 25 patients (37.3%) and finally a spotty (“patchy”) pattern in 2 (2.9%). Among patients with positive LGE, the extent of LGE was 6.3%+/-8.8% of LV mass. Fifty-eight patients underwent to EMB: 33/58 patients (56.9%) showed replacement-type fibrosis, of this subgroup 23 patients (69.7%) showed LGE on CMR. Out of 13/58 patients (22%) without replacement-type fibrosis on EMB, LGE was present in 9/13 (69.2%) patients: in this subgroup the most frequent LGE pattern was midwall/subepicardial stria (n=8/9; 89%) and one patient (11%) showed a “patchy” LGE pattern . Compared to EMB, CMR showed a low accuracy for fibrosis detection. The range of follow-up in LGE group was 8 years-1 month. Kaplan-Meier curves for composite end-point and ventricular arrhythmias showed a significant differences between patients with and without LGE on CMR (Wilcoxon-Breslow: p< 0.05). The amount of LGE%, by univariate analysis, was strongly associated with ventricular arrhythmias (HR 1.05, 95% CI 1.02 to 1.08; p<0.0001). This association was unchanged in multivariate analysis adjusted for a EF<30% (model 5): HR 1.067, 95% CI 1.034 to 1.1; p<0.0001.With an associated HR of 2.5, the presence of LGE was among the strongest multivariate predictors for the combined end point, surpassed only by age < 49 years. ROC curve analysis revealed a LGE percentage of 3.5 as optimal discriminator for the occurrence of ventricular arrhythmic events with an associated HR of 4.11 (95% CI 1.3 to 12.7; p<0.001). Group B: On the basis of clinical and CMR evaluation, 24 patients (46%) were defined as “classic ARVC phenotype”; 14 (27%) as “left dominant phenotype”, and finally 14 (27%) as “biventricular ARVC phenotype”. Comparison between ECG and CMR showed that ECG indexes of LV dilatation are ST-segment elevation and T-wave inversion beyond V3 (p<0.05); among tissue characterization parameters, only LV LGE has an identifiable ECG abnormality, i.e. ST segment elevation (p<0.05). On EVM, endocardial voltages of RV was abnormal in 21/23 (91%) patients, with a total of 45 electroanatomic scars (EAS). RV LGE was found in 9/23 (39%) patients, with a total of 23 RV LGE scars: there was a mismatch in 24 RV scars, with 22 EAS not confirmed by LGE. In 9/12 (75%) patients with abnormal RV EVM/normal RV LGE, ≥1 LGE were identified in the LV. The patients of ARVC group enrolled for the follow-up were 52 (34 males; mean age 33+/-15 years). The mean LV ejection fraction was 57+/-8%; the mean fractional area change of RV was 39+/-10%. The mean follow-up was 25.6 months (range 38+/-4 months). Considering only the major events (aborted sudden death/ ventricular fibrillation; sudden death; non sudden death/heart transplantation) these occurred in 12 (7 in the LGE group, 5 in the non-LGE group).Kaplan-Meier curves did not show difference between LGE presence/absence for all events and major events. Kaplan-Meier curves did not show difference between three phenotypes detected by CMR both for all events and major events. Conclusions: CMR can provide a wide range of information in DCM and ARVC, beyond traditional imaging modalities. In the setting of DCM, CMR shows high accuracy in the detection of non-ischemic aetiology compared with angiography. LGE identifies the patients with increased risk of ventricular arrhythmic events. Compared to EMB, CMR with LGE imaging shows low accuracy for fibrosis detection, probably due to resolution power of CMR. However, an integrated approach with CMR and EMB may be useful in cases with negative EMB/positive LGE to identify epicardial lesion, which are not caught by EMB due to its endocardial approach. In the setting of ARVC, CMR confirms its superiority in assessing the full spectrum of morpho-functional and tissue abnormalities of a disease that should be as a biventricular cardiomyopathy. The ECG indexes able to identify LV dilatation are ST-segment elevation and T-wave inversion beyond V3; as far as tissue characterization parameters are concerned, LV LGE was associated to ST segment elevation. The correlation between EVM and CMR confirms that EVM allows an accurate identification of RV EAS in patients with ARVC and supports its clinical use for substrate-based mapping and catheter ablation of RV tachycardias as well as for imaging-guided EMB. Currently available LGE CMR appears to visualize unsatisfactorily RV scars and this limits its usefulness in ARVC diagnosis and guiding interventional RV procedures. However, the high prevalence of LV involvement in ARVC patients is in keeping with the current perspective of biventricular disease and points out the diagnostic relevance of LV scar detection by LGE CMR.
Introduzione: Le cardiomiopatie rappresentano un gruppo eterogeneo di malattie del muscolo cardiaco la cui caratterizzazione tissutale finora è stata eseguita prevalentemente mediante analisi ex vivo. La risonanza magnetica cardiaca (RMC), grazie all’utilizzo di apposite sequenze e all’impiego di un mezzo di contrasto (gadolinio, visibile come Late Gadolinium Enhancement, LGE), rende possibile una caratterizzazione tissutale in vivo. L’analisi della sede ed estensione dell’LGE permette di differenziare la cicatrice miocardica post-infartuale (LGE sub endocardico o trans murale) rispetto ad altre cicatrici di tipo non ischemico. Nelle diverse cardiomiopatie, il significato prognostico dei depositi di LGE non è del tutto chiarito, se non in parte per la cardiomiopatia ipertrofica. In generale la presenza di LGE nel contesto di una cardiomiopatia viene identificato con la presenza di fibrosi miocardica, nonostante il meccanismo di deposito del gadolinio non sia uguale nelle diverse eziologie di cardiomiopatie, non necessariamente associate a fibrosi miocardica. Nell’ambito delle cardiomiopatie, la cardiomiopatia dilatativa (non dovuta ad una eziologia ischemica) (CMD) si caratterizza da un punto di vista istologico per la presenza di fibrosi interstiziale, con o senza fibrosi sostitutiva, entrambe associate ad una prognosi infausta. Una diversa patologia miocardica in cui la RMC offre una eccezionale capacità di caratterizzazione tissutale è la Cardiomiopatia Aritmogena del Ventricolo Destro (CAVD), una miocardiopatia dovuta ad una progressiva atrofia miocardica con successiva sostituzione fibroadiposa. Benché la RMC stia consolidando il suo ruolo nella pratica clinica, non è stata ancora eseguita una applicazione estensiva della RMC in queste due differenti cardiomiopatie a scopo diagnostico e prognostico, ed ancor più manca una analisi sistematica delle correlazioni tra i diversi quadri radiologici ed i tradizionali parametri invasivi e non-invasivi di queste cardiomiopatie. Scopo dello Studio: al fine di valutare il significato clinico e prognostico dell’LGE nelle CMD e nella CAVD sono state perseguite le seguenti linee di ricerca: 1) nei pazienti affetti da CMD il significato prognostico dell’LGE nelle DCM, con particolare riferimento ad un end-point di eventi combinati ed all’outcome aritmico; 2) nei pazienti affetti da CAVD il confronto tra i diversi aspetti alla RMC ed 1a) i quadri elettrocardiografici; 1b) il confronto con dati ottenuti dal mappaggio endocavitario del ventricolo destro (“Endocardial Voltage Mapping”, EVM); 1c) il significato prognostico dell’LGE; 3) il significato della alterazioni di caratterizzazione tissutale alla RMC confrontati con i dati istologici dei pazienti con biopsia endomiocardica (BEM) o che sono andati incontro a decesso/trapianto cardiaco nei due gruppi. Materiali e Metodi: tra il Gennaio 2007 e il Dicembre 2010 sono stati arruolati prospetticamente i pazienti riferiti presso il nostro Centro per una valutazione invasiva per il riscontro di una dilatazione del ventricolo sinistro (Gruppo CMD, A) o per sospetta CAVD (Gruppo CAVD, B). Gruppo CMD (A): sono stati valutati 210 riferiti per riscontro di dilatazione ventricolare con esordio subacuto-cronico (≥ 1 mese), con o senza pregressa storia di scompenso cardiaco, che durante la stessa ospedalizzazione sono stati sottoposti a coronarografia, RMC con contrasto e BEM. Gruppo CAVD (B): 52 soggetti riferiti presso il nostro Centro per sospetta CAVD e la cui diagnosi è stata raggiunta in accordo con i correnti criteri clinico-strumentali recentemente modificati. Durante la stessa ospedalizzazione sono stati sottoposti RMC con contrasto e studio elettrofisiologico con EVM e BEM in casi selezionati. Ogni paziente appartenente ad entrambi i gruppi è stato sottoposto ad un follow-up clinico-strumentale. Resultati: Gruppo A. Sulla base dei risultati della coronarografia i pazienti sono stati suddivisi in due gruppi in base alla presenza o meno di coronaropatia: in 99 è stato definita una eziologia ischemica alla base della disfunzione ventricolare, 111 non mostravano alcuna coronaropatia (gruppo CMD). Il gruppo dei soggetti ischemici è stato escluso dalla successive analisi. Rispetto all’angiografia coronarica, la RMC ha dimostrato un’ottima accuratezza diagnostica (96.5%) nell’escludere una eziologia ischemica. Nel gruppo A la presenza di un LGE di tipo non-ischemico è stata riscontrata in 67 casi (60.4%) mentre era assente in 44 (39.6%). Nessuna differenza nei volumi ventricolari e funzione sistolica è stata riscontrata nei due sottogruppi. Nei 67 pazienti con LGE era presente un pattern di tipo “gray” in 12, tipo stria “midural”/epicardica in 49 (73.1%), alla giunzione settale tra ventricolo destro e sinistro isolatamente in 4 (5.9%), associato ad altri pattern in 25 (37.3%), ed infine tipo “patchy” in 2 casi (2.9%). Nei pazienti con LGE, l’estensione media era pari al 6.3%+/-8.8% della massa del ventricolo sinistro. In 58 casi è stata eseguita la BEM: 33/58 pazienti (56.9%) mostravano aspetti di fibrosi sostitutiva; di questi, 23/33 (69.7%) mostravano anche LGE alla RMC. In 13/58 casi (22%) si riscontrava una BEM negativa: in questo sottogruppo di soggetti era presente un LGE in 9/13 (69.2%): nella maggioranza dei casi (8/9 pari all’89%) l’LGE era tipo stria “midmural”/epicardica, in uno solo (11%) tipo “patchy”. Nel gruppo A il range del follow-up è 8 anni-1 mese. Le curve di sopravvivenza Kaplan-Meier per eventi combinati ed aritmie ventricolari maggiori hanno mostrato una differenza significativa tra i due gruppi di pazienti con una prognosi peggiore nel gruppo con LGE (Wilcoxon-Breslow: p< 0.05). La quantità totale di LGE si è dimostrata associata alle aritmie ventricolari (HR 1.05, 95% CI 1.02-1.08; p<0.0001); tale correlazione rimaneva anche all’analisi multivariata aggiustata per una frazione d’eiezione inferiore al 30% (HR 1.067, 95% CI 1.034-1.1; p<0.0001).I pazienti con LGE mostravano un rischio di 2.5 per la comparsa di aritmie ventricolari e mediante l’analisi della curva ROC la percentuale di LGE pari a 3.5% è risultato il miglior valore predittivo di eventi aritmici (HR 4.11 (95% CI 1.3-12.7; p<0.001). Gruppo B. Sulla base dei risultati della RMC, 24 soggetti (46%) sono stati definiti affetti da un forma “classica”, 14 (27%) “dominante sinistra”, e 14 (27%) “biventricolare”. Analizzando la correlazione tra ECG e RMC, gli unici predittori della dilatazione del ventricolo sinistro sono risultati la presenza di un sopraslivellamento del tratto ST e le T invertite oltre V3 (p<0.05); nelle sequenze per la caratterizzazione tissutale la presenza di LGE a carico del ventricolo sinistro era associata ad un sopraslivellamento del tratto ST. Dall’analisi di confronto tra mappaggio endocavitario (EVM) e LGE è emerso che in 21/23 (91%) si dimostrava la presenza di un voltaggio ridotto, per un totale di 45 cicatrici elettroanatomiche. La presenza di LGE a carico del ventricolo destro si è riscontrata in 9/23 (39%) casi, per un totale di 23 cicatrici alla RMC: in 24 casi vi è stato un mismatch tra le due metodiche nel riconoscere le cicatrici di sostituzione fibro-adiposa. In 9/12 (75%) dei soggetti con EVM patologico/RMC normale, sono state riscontrate aree di LGE in almeno una regione del ventricolo sinistro. Il follow-up medio dei pazienti con CAVD arruolati nel follow-up (52; 34 maschi; età media 33+/-15 anni) è stato di 25.6 mesi (38+/-4 mesi). Considerando come eventi maggiori la morte cardiaca (abortita o meno), la fibrillazione/tachicardia ventricolare, morte/trapianto cardiaco gli eventi combinati sono stati 12 (7 nel gruppo con LGE e 5 in quelli senza LGE). Non si è dimostrata alcuna differenza in termini di tempo libero da eventi nei tre gruppi. Conclusioni: La RMC nell’ambito dello studio della CMD e della CAVD offre delle capacità diagnostiche al di là delle tradizionali metodiche di imaging. Nella CMD presenta un’ottima accuratezza diagnostica, rispetto alla ventricolo-coronarografia, nell’escludere una eziologia ischemica alla base della dilatazione e disfunzione ventricolare. La presenza di LGE nella DCM è in grado inoltre di individuare i paziente a maggior rischio aritmico. Tuttavia se confrontata con la BEM, l’accuratezza diagnostica della RMC rimane bassa, probabilmente a causa del suo potere di risoluzione spaziale che limita il riconoscimento di piccole aree di fibrosi miocardica. D’altra parte, la RMC è in grado di vedere lesioni epicardiche che non sono raggiunte dalla BEM supportando così l’importanza di una valutazione combinata delle due metodiche nelle CMD. Nei soggetti con CAVD, la RMC si conferma tecnica di imaging capace di esplorare l’intero spettro di alterazioni morfo-funzionali e tissutali della CAVD, che spesso è una malattia bi ventricolare e non può essere esclusiva del ventricolo destro. Il confronto tra ECG e RMC indica la presenza di un sopraslivellamento del tratto ST e l’inversione delle onde T come predittori della dilatazione del ventricolo sinistro; la presenza di LGE a carico del ventricolo sinistro è associato ad un sopraslivellamento del tratto ST. Analizzando i dati relativi al mappaggio elettronatomico, emerge come quest’ultimo riconosca più cicatrici di quanto non riesca a fare la RMC, probabilmente per la difficoltà di riconoscere un LGE a carico della parete assai assottigliata del ventricolo destro. Tuttavia la capacità della RMC di riconoscere le lesioni anche a carico del ventricolo sinistro, laddove il mappaggio elettroanatomico non viene applicato, suggerisce un sinergismo diagnostico tra le due metodiche. Probabilmente il breve tempo di follow-up nel quale si è indagato il significato prognostico dell’LGE a carico del ventricolo sinistro ha reso non significativa la differenza in termini di tempo libero da eventi nei tre gruppi. Studi futuri su casistiche più numerose, tipizzate dal punto di vista genetico e con RMC seriate, delucideranno meglio il significato prognostico di un coinvolgimento precoce del ventricolo sinistro.

Myocardial scar, a non-viable tissue which occurs on the myocardium due to the insufficient blood supply to the heart muscle, is one of the leading causes of life-threatening heart disorders, including arrhythmias. Analysis of myocardial scar is important for predicting the risk of arrhythmia and locations of re-entrant circuits in patients’ hearts. For applications, such as computational modeling of cardiac electrophysiology aimed at stratifying patient risk for post-infarction arrhythmias, reconstruction of the intact geometry of scar is required. Currently, 2D multi-slice late gadolinium-enhanced magnetic resonance imaging (LGEMRI) is widely used to detect and quantify myocardial scar regions of the heart. However, due to the anisotropic spatial dimensions in 2D LGE-MR images, creating scar geometry from these images results in substantial reconstruction errors. For applications requiring reconstructing the intact geometry of scar surfaces, 3D LGE-MR images are more suited as they are isotropic in voxel dimensions and have a higher resolution. While many techniques have been reported for segmentation of scar using 2D LGEMR images, the equivalent studies for 3D LGE-MRI are limited. Most of these 2D and 3D techniques are basic intensity threshold-based methods. However, due to the lack of optimum threshold (Th) value, these intensity threshold-based methods are not robust in dealing with complex scar segmentation problems. In this study, we propose an algorithm for segmentation of myocardial scar from 3D LGE-MR images based on Markov random field based continuous max-flow (CMF) method. We utilize the segmented myocardium as the region of interest for our algorithm. We evaluated our CMF method for accuracy by comparing its results to manual delineations using 3D LGE-MR images of 34 patients. We also compared the results of the CMF technique to ones by conventional full-width-at-half-maximum (FWHM) and signal-threshold-to-reference-mean (STRM) methods. The CMF method yields a Dice similarity coefficient (DSC) of 71 +- 8.7% and an absolute volume error (|VE|) of 7.56 +- 7 cm3. Overall, the CMF method outperformed the conventional methods for almost all reported metrics in scar segmentation. We present a comparison study for scar geometries obtained from 2D vs 3D LGE-MRI. As the myocardial scar geometry greatly influences the sensitivity of risk prediction in patients, we compare and understand the differences in reconstructed geometry of scar generated using 2D versus 3D LGE-MR images beside providing a scar segmentation study. We use a retrospectively acquired dataset of 24 patients with a myocardial scar who underwent both 2D and 3D LGE-MR imaging. We use manually segmented scar volumes from 2D and 3D LGE-MRI. We then reconstruct the 2D scar segmentation boundaries to 3D surfaces using a LogOdds-based interpolation method. We use numerous metrics to quantify and analyze the scar geometry including fractal dimensions, the number-of-connected-components, and mean volume difference. The higher 3D fractal dimension results indicate that the 3D LGE-MRI produces a more complex surface geometry by better capturing the sparse nature of the scar. Finally, 3D LGE-MRI produces a larger scar surface volume (27.49 +- 20.38 cm3) than 2D-reconstructed LGE-MRI (25.07 +- 16.54 cm3).

Gadolinium endohedral metallofullerenes (EMFs) have shown the potential to become next generation magnetic resonance imaging (MRI) contrast agents due to their significantly improved efficiency and safety, as well as multi-day body retention which allows for a longer surgery and observation compared to current contrast agents. In Chapter 1, I have reviewed the development of gadolinium EMF based MRI contrast agents. In Chapter 2, I have described my study of Gd3N@C80 and Gd3N@C84 metallofullerenols as next generation MRI contrast agents. The metallofullerenols are synthesized and characterized utilizing UV-vis, IR, X-ray photoelectron spectroscopy (XPS) and dynamic light scattering (DLS). In addition, relaxivity data were obtained for the two metallofullerenes, and the results showed that Gd3N@C84 metallofullerenol had enhanced relaxivity compared to Gd3N@C80 metallofullerenol. This result is consistent with the observation of magnetic resonance images of the samples at different concentrations. The enhanced relaxivity was attributed to the special "egg shape" of the Gd3N@C84 cage. In Chapter 3, I have described the relaxivity study of Gd3N@C80 (without functionalization) in oleic acid, which could be used as an MRI contrast agent for more hydrophobic bioenvironments. The results show that Gd3N@C80 has a reasonable relaxation effect (relaxivity ~10 mM-1S-1 at 1.4 T) in oleic acid and could be a viable contrast agent even without functionalization. In Chapter 4, I have discussed the outlook of gadolinium EMF-based MRI contrast agents and suggested several directions for future work.
Master of Science

La première partie de cette thèse porte sur l'étude du no-reflow ou obstruction microvasculaire en IRM cardiaque. Dans une première étude, nous avons mesuré l'incidence du no-reflow dans une population de 25 patients pris en charge pour infarctus du myocarde sans sus-décalage du segment ST. Nous avons trouvé que 32% de ces patients présentaient un no-reflow et que la présence de no-reflow était associée à une taille d'infarctus significativement plus importante ainsi qu'une élévation plus importante des enzymes cardiaques. Dans une deuxième étude nous avons comparé la performance diagnostique du myocardial blush grade (MBG) pour le diagnostic du no-reflow avec l'IRM cardiaque sur les séquences de rehaussement tardif post-gadolinium. Cette étude a été réalisée dans une population de 39 patients pris en charge pour un premier épisode de STEMI. Nous avons trouvé que le MBG sous-estimait la présence de no-reflow à la phase aiguë de l'infarctus après reperfusion optimale en comparaison avec l'IRM. La deuxième partie de cette thèse concerne la quantification de l'infarctus du myocarde en IRM cardiaque de rehaussement tardif post-gadolinium. Nous avons comparé une technique d'évaluation semi-quantitative visuelle rapide avec la planimétrie manuelle classique sur une population de 103 patients pris en charge pour syndrome coronarien aigu. La taille de l'infarctus était évaluée par ces deux méthodes en IRM cardiaque réalisée 4 jours après admission. Nous avons trouvé une excellente corrélation et un bon niveau de concordance entre les deux méthodes d'évaluation de la taille d'infarctus, avec des temps de posttraitements beaucoup plus courts pour l'analyse visuelle rapide. Enfin, la troisième partie de cette thèse aborde le sujet de l'utilisation de l'IRM cardiaque comme outil de mesure dans les essais thérapeutiques sur la reperfusion myocardique. Nous avons utilisé l'IRM cardiaque pour évaluer l'efficacité de l'utilisation de la cyclosporine A à la phase aigüe de l'infarctus reperfusé et son effet sur remodelage ventriculaire à 6 mois. Dans cette étude 28 patients ont été étudiés en IRM cardiaque 5 jours et 6 mois après un infarctus du myocarde. Nous avons trouvé une persistance de la réduction significative de 23% de taille de l'infarctus à 6 mois dans le groupe traité par cyclosporine par rapport au groupe contrôle. Il n'y avait pas d'effet négatif de la cyclosporine A sur le processus de remodelage ventriculaire gauche
We assessed the presence and extent of microvascular obstruction (MVO) and its relationship with infarct size and left ventricular (LV) functional parameters after acute non-ST elevated myocardial infarction (NSTEMI). 25 patients with first acute NSTEMI underwent a complete cardio magnetic resonance (CMR) study 72 hours after admission. MO was detected in 32% of patients and was significantly associated with a larger infarct size. There were no significant difference between both groups for the LV functional parameters but patients with MO showed a higher troponin-I and CK release. We studied the relation between Myocardial Blush Grade (MBG) and gadolinium-enhanced CMR for the assessment of MVO in 39 patients with acute ST elevated myocardial infarction (STEMI) treated by primary PCI. No statistical relation was found between MBG and MVO extent at CMR (p=0.63). MBG underestimates MVO after an optimal revascularization in AMI compared to CMR.We compared the performance and post-processing time of a global visual scoring method to standard quantitative planimetry and we compared both methods to the peak values of myocardial biomarkers. 103 patients admitted with reperfused AMI to our intensive care unit had a complete CMR study 4±2 days after admission. There was an excellent correlation between quantitative planimetry and visual global scoring for the hyperenhancement extent’s measurement (r=0.94; y=1.093x+0.87; SEE=1.2; P<0.001) and there was also a good concordance between the two approaches with significantly shorter mean post-processing time for the visual scoring method. There was also significant levels of correlation between the enzymatic peak values and the visual global scoring method. The visual global scoring method allows a rapid and accurate assessment of the myocardial global delayed enhancement. This study examined the effect of a single dose of cyclosporine A used at the time of reperfusion, on LV remodeling and function by cardiac magnetic resonance (CMR) in the early days and 6 months after AMI.28 patients of the original cyclosporine A study had an acute (day 5) and a follow-up (6 months) CMR study. There was a persistent 23% reduction of the absolute infarct size at 6 months without any dementrial effect in the cyclosporine A group compared with the control group of patients. Cyclosporine A used at the moment of AMI reperfusion persistently reduces infarct size and does not have a detrimental effect on LV remodeling

This thesis deals with the synthesis of dendritic gadolinium complexes based on DOTA, with a view to obtaining enhanced relaxivities. Li addition to the inherently long electronic relaxation time and high paramagnetic moment of the gadolinium (III) ion, the speed of rotation of its complexes in solution is a decisive parameter in the determination of the relaxivity. This parameter is dependent on the molecular mass of the complex. Initially, the enantioselective synthesis of novel a-substituted analogues of DOTA was attempted but was not successful due to difficulties encountered in attaining the tetraalkylation of cyclen and the purification of the products obtained. Therefore, further studies were carried out based on the known [Gd(gDOTA)]" system. The synthesis of three medium M(_W) dendrons, each with a focal primary amino group was carried out. Their structures may be described as dendrimeric analogues of poly(ethylene glycol). Two of these structures were successfully coupled to the gadolinium (III) chelate, [Gd.gDOTA]. The acid-catalysed epimerisation of the statistical distribution of stereoisomers yielded solely the (RRRR)/(SSSS) isomeric pair. This system had previously been shown to undergo fast water exchange. The coupling and deprotection procedure yielded paramagnetic dendritic complexes with molecular weights of 2013 and 3535.Relaxivity measurements were carried out on these systems and the results showed significantly higher relaxivities of 18 and 21 mM(^-1) s(^-1) respectively, compared with a value of 7.8 mM(^-1) s(^-1) for the parent compound. Examination of NMRD profiles for the larger system showed a decrease in the rotational correlation time to 310 ps at 298 K, as expected. However, this was accompanied by an increase in the inner-sphere water exchange lifetime to 570 ns at 298 K. Therefore, although an improvement in relaxivity was obtained through a coupling to the slower rotation of the system in solution, this enhancement was limited by the accompanying decrease in the rate of water exchange. The best fitting procedure of the NMRD profiling procedure revealed the presence of 8 second-sphere water molecules at an average distance of 4Å. The second sphere contribution was shown to be the dominant contributor to the overall relaxivity. This accounted for >50% of the increased relaxivity.

Cardiovascular magnetic resonance imaging (CMR) has become one of the great pillars of cardiac imaging. Modern CMR, as we now practise it, is the result of an enormous method and application development effort that has occurred over the past 25 years and has taken CMR from its humble beginnings of anatomical T₁- and T₂-weighted imaging to the extremely versatile, accurate, and robust technique it is now. The main developments over this time, building on the anatomical imaging, were the establishment of cine imaging for assessment of cardiac function, first-pass perfusion imaging for measurement of perfusion reserve, as well as myocardial blood flow (in millilitres per minute and gram), late gadolinium enhancement for imaging of scar and patchy fibrosis, and two-dimensional flow velocity imaging for assessment of valve and shunt lesions. This textbook intends to explore and evaluate all areas of this fascinating subject.

Magnetic resonance imaging (MRI) provides excellent anatomic detail and soft tissue contrast for the evaluation of patients with renal disease. MRI needs longer scan time than computed tomography (CT); however, no radiation is involved. Gadolinium-based contrast agents (GBCAs) are used to help provide additional image contrast during MRI. MRI is indicated for characterization of renal mass, staging of malignant renal neoplasms, and determination of vena cava involvement by the renal tumour. Magnetic resonance (MR) angiography is widely accepted as a non-invasive imaging work-up of renal artery stenosis. MR urography is an alternative to CT urography to assess the upper urinary tract but does not identify urinary calculi. Diffusion-weighted imaging is a functional MR technique being used to characterize parenchymal renal disease and renal tumours. Nephrogenic systemic fibrosis is a rare but debilitating and potentially life-threatening condition which has been linked to exposure of GBCAs in patients with severe renal insufficiency. The risk versus benefit must be assessed before proceeding.

In general, ultrasonography and magnetic resonance imaging (MRI) are not associated with maternal or fetal risks and are the imaging techniques of choice for the pregnant patient. Ultrasound is the mainstay of obstetric imaging because it is safe and easily performed. However, MRI is becoming more useful as an adjunct in cases of questionable ultrasound findings or if additional information is needed to plan patient care. MRI lacks the potential risks of ionizing radiation associated with other forms of imaging and, when needed, gadolinium can be used (however, use remains uncommon in current practice). For maternal evaluation in patients with neuromuscular disorders MRI is ideal for imaging. Nevertheless, any imaging (either maternal or fetal) should be used only when needed. Furthermore, if other imaging modalities (CT, MRI with contrast, etc.) are better for assessing the mother’s or fetus’s condition and the information will influence the pregnancy care, these should be utilized.

Case report: Male, 32-year-old, diagnosed with COVID-19 (coronavirus disease) in January 2022 and two weeks later present progressive vertigo, gait instability, binocular diplopia and right facial palsy. Three months later he was sent for investigation in our service. Magnetic resonance imaging (MRI) showed a FLAIR-hyperintense lesion in the pontomesencephalic transition with gadolinium enhancement. Cerebrospinal fluid (CSF) analysis shows increase in protein level (83 mg/dL). In this moment, considering the infectious antecedent and MRI characteristics, he has been diagnosed with acute disseminated encephalomyelitis (ADEM) and submitted to pulse therapy with methylprednisolone, showing complete improve of symptoms. In outpatient follow-up he presents with worsening of symptoms. Ten months after onset of symptoms he was hospitalized again, MRI showed new lesions on medulla and cerebellum. Submitted to pulse therapy followed by plasma exchange, with no improve. New MRI presents with infiltrative lesion without gadolinium enhancement. CSF analysis show 48 cells (98% lymphocytes), no evidence of neoplastic cells. A biopsy was performed on the lesion and showed atypical lymphoid infiltrate with B-Cells predominance, positive to CD20 and CD45, confirming diagnosis of Primary CNS Lymphoma (PCNSL). Initiated chemotherapy, but unfortunately patient die in consequence of neutropenia. Discussion: PCNSL is an uncommon neoplasm and rarely affects brainstem. When it occurs the prognosis is poor, nearly half of patients died within 1 year after diagnosis. Glucocorticoids could promote tumor shrinkage. Neuroimaging characteristics could be confounding with infections, demyelinating lesions, and gliomas. Conclusion: Our case illustrates a patient initially diagnosed with ADEM and submitted to corticotherapy with good response, however he worse in months later and the diagnosed reviewed to PCNSL. This shows the importance of considering atypical PCNSL in differential diagnosis of demyelinating diseases.

Case presentation: We describe the case of a 75-year-old female, with no past relevant comorbidities. The onset was of mental confusion and imbalance, within two weeks progressing to dysphonia, dysphagia and spastic quadriparesis. Brain MRI showed hyperintense T2/FLAIR (T2-weighted-FluidAttenuated Inversion Recovery) lesions in white matter, with cortical sparing, restricted diffusion and gadolinium enhancement. Demyelinating diseases and central nervous system lymphoma hypothesis were made. Two months later a brain biopsy was performed. Diffuse white matter vacuolar impairment was found and no inflammatory infiltrate, resembling Canavan’s disease. The patient had progressive clinical worsening, with prolonged hospitalization and poor general condition at discharge, not enduring further investigation. She deceased after 8 months of symptoms onset. Discussion: The diagnosis of acute leukoencephalopathies is challenging and neuroimaging may be helpful. Diffusion, contrast enhancement and corticosubcortical relation in magnetic resonance imaging (MRI) can present valuable clues. In this case, for example, acute disseminated encephalomyelitis was less likely due to the MRI evidencing dissemination in time. To better address malignancy, brain biopsy was mandatory. Not only cancer was excluded, but the demyelination was revealed to possibly be neurodegenerative, which was neither clinically nor radiographically evident. The vacuolar pattern found is described in Canavan disease, a rare leukoencephalopathy with onset at 1–4 months age, and mean survival of months to few years. In literature there is only another report, cataloged in our Pathology department, of a 43-yearold male with similar clinical, imaging and histological findings. This case may illustrate a not yet cataloged disease, maybe an unknown presentation of Canavan disease spectrum, adding one more differential diagnosis for acute leukoencephalopathies.

A 66-year-old woman, newly diagnosed with a gastric adenocarcinoma with signet-ring cells, presented with bilateral retro-orbital pain, with worsening eye movement. After seven days, she developed a loss of visual acuity in the right eye, with an altitudinal pattern and rapid evolution to amaurosis. A week later, she noticed the loss of contralateral visual acuity, with field constriction. She sought an ophthalmologist, who performed fundoscopy, finding occlusion of the central retinal vein on the right and bilateral papillary edema. Prednisone 60 mg was prescribed for seven days. Due to a lack of improvement, she searched our service for evaluation. Examination findings revealed only light perception in the left eye and no light perception in the right eye. A bilateral absolute afferent defect was also found. Fundoscopy revealed bilateral papillary edema. Magnetic resonance imaging revealed thickening of the optic nerves and chiasm, with diffusion restriction, in addition to FLAIR hyper signal next to the optic nerve sheath, which exhibits gadolinium enhancement with densification of the surrounding intraorbital fat. This may represent a metastatic spread of the underlying disease. Cerebrospinal fluid analysis showed 4 cells, with 33% of neoplastic cells. Glucose and protein values were within normal range and cultures for both bacteria and fungi were negative. Blood test findings were unremarkable. Computed tomography of the abdomen showed diffuse gastric thickening, in addition to a left adrenal lesion suggestive of secondary involvement. The patient was referred to an oncology service for treatment and followup of metastatic gastric neoplasia. Few cases of metastatic involvement of the optic nerve are reported in the literature. Therefore, the cautious approach of a patient with visual loss and cancer history would avoid misdiagnosis.

Review question / Objective: The objectives of this systematic review were to evaluate the efficacy and safety of the three existing anti-CD20 antibodies for the treatment of relapsing multiple sclerosis and to aid clinicians in choosing medications. Eligibility criteria: We set the inclusion criteria as follows: (1) study type: RCT; (2) language restriction: only available in English; (3) participants: patients ≥18 years of age diagnosed with relapsing MS, whether with a relapsing–remitting course or a secondary progressive course; (4) intervention: anti-CD20 antibody treatments including ocrelizumab, ofatumumab, rituximab, and corresponding control including placebo and active treatments; (5) outcomes: clinical outcomes including annualized rate of relapse (ARR), the number of patients free of relapse, and the number of patients with confirmed disease progression (CDP); magnetic resonance imaging(MRI) outcomes including gadolinium-enhancing lesion change in T1, change in the volume of lesions on T2, the number of patients with no new or newly enlarged lesions in T2 and the brain volume change (BVC); safety outcomes including adverse events (AEs) and serious adverse events (SAEs). Included RCTs were not requested to supply all the outcomes mentioned above. We set the exclusion criteria as follows: (1) study type: retrospective studies, cohort studies, case reviews and case reports; (2) patients diagnosed with primary progressive MS.