Translation of Carbon-13 EPI for hyperpolarized MR molecular imaging of prostate and brain cancer patients

Abstract

Purpose: To develop and translate a metabolite-specific imaging sequence using a symmetric echo planar readout for clinical hyperpolarized (HP) Carbon-13 (¹³ C) applications.

Methods: Initial data were acquired from patients with prostate cancer (N = 3) and high-grade brain tumors (N = 3) on a 3T scanner. Samples of [1-¹³ C]pyruvate were polarized for at least 2 h using a 5T SPINlab system operating at 0.8 K. Following injection of the HP substrate, pyruvate, lactate, and bicarbonate (for brain studies) were sequentially excited with a singleband spectral-spatial RF pulse and signal was rapidly encoded with a single-shot echo planar readout on a slice-by-slice basis. Data were acquired dynamically with a temporal resolution of 2 s for prostate studies and 3 s for brain studies.

Results: High pyruvate signal was seen throughout the prostate and brain, with conversion to lactate being shown across studies, whereas bicarbonate production was also detected in the brain. No Nyquist ghost artifacts or obvious geometric distortion from the echo planar readout were observed. The average error in center frequency was 1.2 ± 17.0 and 4.5 ± 1.4 Hz for prostate and brain studies, respectively, below the threshold for spatial shift because of bulk off-resonance.

Conclusion: This study demonstrated the feasibility of symmetric EPI to acquire HP ¹³ C metabolite maps in a clinical setting. As an advance over prior single-slice dynamic or single time point volumetric spectroscopic imaging approaches, this metabolite-specific EPI acquisition provided robust whole-organ coverage for brain and prostate studies while retaining high SNR, spatial resolution, and dynamic temporal resolution.

Keywords: DNP; EPI; hyperpolarization; oncology; pyruvate.

Figure 1.

Multi-slice echoplanar pulse sequence. The complex singleband spectral-spatial pulse (real and imaginary RF shown) is used to selectively excite an individual hyperpolarized metabolite. An entire volume is acquired for one metabolite before switching to the next frequency. An optional delay can be added after all metabolite volumes are acquired to achieve the desired temporal resolution.

Figure 2.

Anatomic ¹H T₂W and ADC maps, and ¹³C pyruvate and lactate area under the curve (AUC) maps for the 6 central slices covering the entire prostate, from the base to the apex. No Nyquist ghost artifacts or geometric distortion were observed in the ¹³C data. There is good spatial agreement between elevated hyperpolarized lactate and regions of low ¹H ADC (indicated by red arrows), consistent with biopsy-proven Gleason 3+4 cancer.

Figure 3.

Pyruvate, lactate, and bicarbonate area under the curve (AUC) maps for the 8 slices covering the entire brain. The red arrowheads indicate the external ¹³C urea phantom, ¹H FLAIR abnormality, and resection cavity, respectively. ¹³C data have been zero-filled fourfold for display. For anatomic reference, ¹H T2 FLAIR images are shown below.

Figure 4.

Pyruvate, lactate, and bicarbonate AUC maps overlaid on ¹H T₂W images. The AUC maps reflect pyruvate uptake and metabolism over the course of the experiment, with lactate metabolism observed throughout the brain and subcutaneous tissues. Conversion to bicarbonate demonstrated a different spatial distribution, with highest signal in gray matter and relatively lower intensities in white matter and subcutaneous tissues. ¹³C data were sinc-interpolated to match the resolution of the ¹H images, and AUCs were normalized to the peak pyruvate intensity.