What is T2* (Transverse Relaxation Time) Magnetic Resonance Imaging in the context of a patient with beta thalassemia major?

What is T2* MRI in Beta Thalassemia Major?

T2 MRI is a specialized cardiac magnetic resonance imaging technique that quantitatively measures myocardial iron deposition by detecting how quickly the heart muscle signal decays in the presence of iron, measured in milliseconds—the lower the T2 value, the greater the cardiac iron overload.** 1

Technical Mechanism

T2* (pronounced "T2-star") represents the time constant for signal decay using gradient echo (GE) sequences, specifically measuring the time taken for the myocardial signal to decay by 63% 1. The fundamental principle relies on iron's paramagnetic properties:

• In non-iron overloaded hearts: MRI signals remain homogenous and relaxation time lasts longer, keeping images brighter over time 1
• In iron overloaded hearts: Iron's paramagnetic effect creates local magnetic field inhomogeneities that shorten relaxation time and darken the image more quickly 1
• The relationship: T2* is inversely proportional to iron content—more iron means shorter T2* values (faster signal decay) 1

The mathematical relationship is expressed as: 1/T2* = 1/T2 + 1/T2′, where T2′ represents magnetic field inhomogeneity caused by iron deposits 1.

Clinical Significance and Critical Thresholds

Cardiac T2 <10 ms is the most important predictor of heart failure development and represents severe cardiac iron overload requiring urgent intervention.* 1

The American Heart Association defines the following risk stratification 1:

• T2 <10 ms*: Severe cardiac siderosis with high risk of cardiac events (heart failure, arrhythmias, cardiac death)
• T2 10-20 ms*: Mild to moderate cardiac iron overload requiring intensified chelation
• T2 >20 ms*: Normal or minimal cardiac iron, though values should ideally be maintained above this threshold

Research demonstrates that all patients with ventricular dysfunction had myocardial T2* <20 ms, and cardiac events occurred in 5/11 patients with T2* <10 ms versus 0/19 patients with T2* >10 ms 2.

Why T2* is Superior to Other Methods

T2 gradient echo technique is preferred over spin echo (T2) sequences because it has greater sensitivity to iron deposition, better signal-to-noise ratio at longer echo times, and superior accuracy for quantifying myocardial iron.* 1

Key advantages include:

• Non-invasive quantification: MRI is the only presently available noninvasive method with potential to assess myocardial iron load quantitatively 1
• Superior to serum ferritin and liver iron: These traditional markers are not adequate surrogates for cardiac iron measurement, as cardiac and hepatic iron loading can occur independently 1
• High reproducibility: Inter-study reproducibility coefficient of variation is only 5% 1
• Prognostic value: Progressive decline in ejection fraction correlates with increasing myocardial iron deposition as measured by T2* 1

Technical Specifications and Scanning Protocol

All clinical T2 MR measurements should be performed at 1.5 Tesla field strength, as this is the only validated standard for clinical use in thalassemia major.* 1

The American Heart Association specifies 1:

• Field strength: 1.5T only (3T scanners show shorter T2* values and greater artifact potential with insufficient clinical validation)
• Acquisition: Single short-axis mid-ventricular slice acquired at multiple echo times (typically 9 separate TEs)
• Breath-hold: Each slice acquired during approximately 20-second breath hold
• Modern technique: Multi-gradient echo sequences allow all slices in one breath hold, reducing scan time 1
• Analysis location: Mid-ventricular septum is the standard measurement site, serving as a good marker of entire myocardial iron content 1

Critical Clinical Pitfalls

Cardiac iron loading and hepatic iron loading do not correlate reliably—patients can have severe cardiac siderosis with relatively normal liver iron concentration, making cardiac T2 measurement essential and irreplaceable.* 1, 2

Important caveats include:

• No correlation with ferritin: Serum ferritin levels >2500 mg/L do not predict cardiac T2* <10 ms or cardiac events 2
• Liver iron dissociation: No significant correlation exists between liver iron concentration and cardiac T2* values 2, 3, 4
• Regional limitations: Accuracy is currently limited to the septum due to susceptibility artifacts from cardiac veins and lungs contaminating other left ventricular walls 1
• Software validation: Only clinically validated software with safeguards against incorrect data handling should be used for analysis 1

Monitoring and Response to Therapy

Patients with severe cardiac siderosis (T2 <10 ms) require at least 5 years of optimal chelation to achieve significant improvement, while those with mild-moderate siderosis (T2 10-20 ms) show significant improvement by year 3.** 5

Longitudinal studies demonstrate 3, 5:

• Severe siderosis: Cardiac T2* improves from mean 6.9-8.5 ms at baseline to 13.6-33.9 ms by year 5 with intensive chelation
• Mild-moderate siderosis: Cardiac T2* improves from mean 14.6 ms to 26.3 ms by year 3
• No correlation: Changes in cardiac T2* do not correlate with changes in liver iron concentration or left ventricular ejection fraction during treatment 5
• Maintenance: Patients without cardiac siderosis maintain T2* >20 ms throughout observation with appropriate chelation 5