To implement and evaluate Convex Optimized Diffusion Encoding (CODE) gradient waveforms for bulk motion compensated cardiac Diffusion Weighted MRI (cDWI) with minimum TEs.cDWI has the potential to characterize cardiac microstructure without the need for a Gadolinium-based contrast agent (GBCA), which is important for the large number of patients with poor renal function requiring evaluation by cardiac MRI[1]. The clinical utility of cDWI, however, has been limited by severe sensitivity to cardiac motion. Recent reports of motion compensated (MOCO) diffusion encoding gradients with nulled first (M₁) and second (M₂) moments have demonstrated robustness to bulk cardiac motion[2, 3], but they necessarily increase the echo time (TE) compared to monopolar encoding (MONO). Increased TEs reduce SNR and limit spatial resolution. We have developed a MOCO cDWI sequence that employs Convex Optimized Diffusion Encoding (CODE) to reduce bulk motion sensitivity and shorten TE compared to existing MOCO schemes.

Gradient Design: CODE diffusion encoding gradients were designed using convex optimization to determine the M1 and M2 nulled gradient waveform that minimizes TE for a target b-value while conforming to hardware constraints (G_Max=74mT/m and SR_Max=50T/m/s) and pulse sequence timing.

Healthy Volunteer Imaging: Healthy volunteers (N=10) were scanned on a 3.0T scanner (Siemens Prisma) after providing written informed consent. High resolution cDWI were acquired in the left ventricular (LV) short-axis with b=350s/mm², 1.5x1.5x5.0mm spatial resolution, 2x GRAPPA acceleration, three orthogonal diffusion encoding directions and three signal averages in a single 15-heartbeat breath hold. Both MONO (TE/TR=67ms/1R-R) and CODE-M₁M₂ encoding (TE/TR=76ms/1R-R) were acquired at eight subject-specific cardiac phases distributed across systole and diastole.

Reconstruction and Data Analysis: Apparent diffusion coefficient (ADC) maps were reconstructed for each cardiac phase. Motion corrupted voxels were identified by ADC values exceeding 3.0x10^-3mm²/s (the diffusivity of free water at 37°C, a thermodynamic upper bound for soft tissues) in the LV. The mean myocardial LV ADC and the percentage of motion corrupted LV voxels were then calculated for each phase. Statistical analyses were performed using t-tests with Holm-Sidak post hoc corrections.

Clinical Imaging: Patients (N=5) undergoing routine clinical cardiac MRI exams were also scanned after providing written informed consent. cDWI were acquired before and after the injection of a GBCA (Gadovist, Bayer Healthcare) using the CODE-M₁M₂ cDWI protocol at a single early systolic phase (100ms delay from the QRS complex via ECG). Mean myocardial LV ADC was calculated after manual segmentation for each patient.

The TE for CODE-M₁M₂ (TE=76ms) was 19% shorter than modified bipolar MOCO[3] (TE=94ms) for 1.5x1.5mm in-plane resolution and b=350s/mm² (Figure 1). With MONO the mean ADC values were significantly corrupted (>3.0x10^-3mm²/s, p<0.004) for 50% of the cardiac phases whereas 0% of the cardiac phases were corrupted with CODE-M₁M₂ (p=N.S.) (Fig. 2B). CODE-M₁M₂ measured significantly lower mean ADCs than MONO (1.9±0.3x10^-3mm²/s vs. 3.8±0.6x10^-3mm²/s, p<0.007) and fewer motion corrupted voxels (14±14% vs 67±21%, p<0.0006) in 100% of the cardiac phases (Fig. 2C).

The clinical CODE-M₁M₂ cDWI scans were largely free of bulk motion artifacts (Fig. 3) and ADC maps were in agreement with myocardial diffusivities measured in volunteers. There was no significant difference between mean ADCs measured pre- and post-contrast (mean ADC_Pre=1.46±0.2x10^-3mm²/s, ADC_Post=1.58±0.3x10^-3mm²/s, P=N.S.).

The volunteer study demonstrated that cDWI with CODE-M₁M₂ mitigated bulk motion artifacts and substantially increased the range of cardiac phases that can accommodate robust ADC measurement. While previous approaches which have required careful selection of the sequence timing and several repeated acquisitions[4], CODE-M₁M₂ was successful for all patients imaged using a single, predetermined 100ms ECG delay. These findings echo previous reports[3, 5, 6] of cDWI with M₁M₂ nulled encoding. Myocardial ADC values (1.4 to 1.6x10^-3mm²/s) were also in agreement with these reports. The agreement in ADC values between pre- and post-contrast imaging highlights the relatively weak T1 dependence of the sequence for characterizing myocardial microstructure, which is important for the interpretation of ADC values in patients that may not receive contrast.CODE-M₁M₂ cDWI significantly improved robustness to cardiac bulk motion compared to MONO cDWI. CODE-M₁M₂ cDWI also permits first and second moment nulling with a shorter TE than existing MOCO cDWI methods.