Simultaneous PET/MRI with (13)C magnetic resonance spectroscopic imaging (hyperPET): phantom-based evaluation of PET quantification.

BACKGROUND: Integrated PET/MRI with hyperpolarized (13)C magnetic resonance spectroscopic imaging ((13)C-MRSI) offers simultaneous, dual-modality metabolic imaging. A prerequisite for the use of simultaneous imaging is the absence of interference between the two modalities. This has been documented for a clinical whole-body system using simultaneous (1)H-MRI and PET but never for (13)C-MRSI and PET. Here, the feasibility of simultaneous PET and (13)C-MRSI as well as hyperpolarized (13)C-MRSI in an integrated whole-body PET/MRI hybrid scanner is evaluated using phantom experiments. METHODS: Combined PET and (13)C-MRSI phantoms including a NEMA [(18)F]-FDG phantom, (13)C-acetate and (13)C-urea sources, and hyperpolarized (13)C-pyruvate were imaged repeatedly with PET and/or (13)C-MRSI. Measurements evaluated for interference effects included PET activity values in the largest sphere and a background region; total number of PET trues; and (13)C-MRSI signal-to-noise ratio (SNR) for urea and acetate phantoms. Differences between measurement conditions were evaluated using t tests. RESULTS: PET and (13)C-MRSI data acquisition could be performed simultaneously without any discernible artifacts. The average difference in PET activity between acquisitions with and without simultaneous (13)C-MRSI was 0.83 (largest sphere) and -0.76 % (background). The average difference in net trues was -0.01 %. The average difference in (13)C-MRSI SNR between acquisitions with and without simultaneous PET ranged from -2.28 to 1.21 % for all phantoms and measurement conditions. No differences were significant. The system was capable of (13)C-MRSI of hyperpolarized (13)C-pyruvate. CONCLUSIONS: Simultaneous PET and (13)C-MRSI in an integrated whole-body PET/MRI hybrid scanner is feasible. Phantom experiments showed that possible interference effects introduced by acquiring data from the two modalities simultaneously are small and non-significant. Further experiments can now investigate the benefits of simultaneous PET and hyperpolarized (13)C-MRI in vivo studies.

Simultaneous Hyperpolarized 13C-Pyruvate MRI and 18F-FDG PET (HyperPET) in 10 Dogs with Cancer.

UNLABELLED: With the introduction of combined PET/MR spectroscopic (MRS) imaging, it is now possible to directly and indirectly image the Warburg effect with hyperpolarized (13)C-pyruvate and (18)F-FDG PET imaging, respectively, via a technique we have named hyperPET. The main purpose of this present study was to establish a practical workflow for performing (18)F-FDG PET and hyperpolarized (13)C-pyruvate MRS imaging simultaneously for tumor tissue characterization and on a larger scale test its feasibility. In addition, we evaluated the correlation between (18)F-FDG uptake and (13)C-lactate production. METHODS: Ten dogs with biopsy-verified spontaneous malignant tumors were included for imaging. All dogs underwent a protocol of simultaneous (18)F-FDG PET, anatomic MR, and hyperpolarized dynamic nuclear polarization with (13)C-pyruvate imaging. The data were acquired using a combined clinical PET/MR imaging scanner. RESULTS: We found that combined (18)F-FDG PET and (13)C-pyruvate MRS imaging was possible in a single session of approximately 2 h. A continuous workflow was obtained with the injection of (18)F-FDG when the dogs was placed in the PET/MR scanner. (13)C-MRS dynamic acquisition demonstrated in an axial slab increased (13)C-lactate production in 9 of 10 dogs. For the 9 dogs, the (13)C-lactate was detected after a mean of 25 s (range, 17-33 s), with a mean to peak of (13)C-lactate at 49 s (range, 40-62 s). (13)C-pyruvate could be detected on average after 13 s (range, 5-26 s) and peaked on average after 25 s (range, 13-42 s). We noticed concordance of (18)F-FDG uptake and production of (13)C-lactate in most, but not all, axial slices. CONCLUSION: In this study, we have shown in a series of dogs with cancer that hyperPET can easily be performed within 2 h. We showed mostly correspondence between (13)C-lactate production and (18)F-FDG uptake and expect the combined modalities to reveal additional metabolic information to improve prognostic value and improve response monitoring.

Simultaneous hyperpolarized (13)C-pyruvate MRI and (18)F-FDG-PET in cancer (hyperPET): feasibility of a new imaging concept using a clinical PET/MRI scanner.

In this paper we demonstrate, for the first time, the feasibility of a new imaging concept - combined hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic imaging (MRSI) and (18)F-FDG-PET imaging. This procedure was performed in a clinical PET/MRI scanner with a canine cancer patient. We have named this concept hyper PET. Intravenous injection of the hyperpolarized (13)C-pyruvate results in an increase of (13)C-lactate, (13)C-alanine and (13)C-CO2 ((13)C-HCO3) resonance peaks relative to the tissue, disease and the metabolic state probed. Accordingly, with dynamic nuclear polarization (DNP) and use of (13)C-pyruvate it is now possible to directly study the Warburg Effect through the rate of conversion of (13)C-pyruvate to (13)C-lactate. In this study, we combined it with (18)F-FDG-PET that studies uptake of glucose in the cells. A canine cancer patient with a histology verified local recurrence of a liposarcoma on the right forepaw was imaged using a combined PET/MR clinical scanner. PET was performed as a single-bed, 10 min acquisition, 107 min post injection of 310 MBq (18)F-FDG. (13)C-chemical shift imaging (CSI) was performed just after FDG-PET and 30 s post injection of 23 mL hyperpolarized (13)C-pyruvate. Peak heights of (13)C-pyruvate and (13)C-lactate were quantified using a general linear model. Anatomic (1)H-MRI included axial and coronal T1 vibe, coronal T2-tse and axial T1-tse with fat saturation following gadolinium injection. In the tumor we found clearly increased (13)C-lactate production, which also corresponded to high (18)F-FDG uptake on PET. This is in agreement with the fact that glycolysis and production of lactate are increased in tumor cells compared to normal cells. Yet, most interestingly, also in the muscle of the forepaw of the dog high (18)F-FDG uptake was observed. This was due to activity in these muscles prior to anesthesia, which was not accompanied by a similarly high (13)C-lactate production. Accordingly, this clearly demonstrates how the Warburg Effect directly can be demonstrated by hyperpolarized (13)C-pyruvate MRSI. This was not possible with (18)F-FDG-PET imaging due to inability to discriminate between causes of increased glucose uptake. We propose that this new concept of simultaneous hyperpolarized (13)C-pyruvate MRSI and PET may be highly valuable for image-based non-invasive phenotyping of tumors. This methods may be useful for treatment planning and therapy monitoring.

Genetic analyses of the human eye colours using a novel objective method for eye colour classification.

In this study, we present a new objective method for measuring the eye colour on a continuous scale that allows researchers to associate genetic markers with different shades of eye colour. With the use of the custom designed software Digital Iris Analysis Tool (DIAT), the iris was automatically identified and extracted from high resolution digital images. DIAT was made user friendly with a graphical user interface. The software counted the number of blue and brown pixels in the iris image and calculated a Pixel Index of the Eye (PIE-score) that described the eye colour quantitatively. The PIE-score ranged from -1 to 1 (brown to blue). The software eliminated the need for user based interpretation and qualitative eye colour categories. In 94% (570) of 605 analyzed eye images, the iris region was successfully extracted and a PIE-score was calculated. A very high correlation between the PIE-score and the human perception of eye colour was observed. The correlations between the PIE-scores and the six IrisPlex SNPs (HERC2 rs12913832, OCA2 rs1800407, SLC24A4 rs12896399, TYR rs1393350, SLC45A2 rs16891982 and IRF4 rs12203592) were analyzed in 570 individuals. Significant differences (p<10(-6)) in the PIE-scores of the individuals typed as HERC2 rs12913832 G (PIE=0.99) and rs12913832 GA (PIE=-0.71) or A (PIE=-0.87) were observed. We adjusted for the effect of HERC2 rs12913832 and showed that the quantitative PIE-scores were significantly associated with SNPs with minor effects (OCA2 rs1800407, SLC24A4 rs12896399 and TYR rs1393350) on the eye colour. We evaluated the two published prediction models for eye colour (IrisPlex [1] and Snipper[2]) and compared the predictions with the PIE-scores. We found good concordance with the prediction from individuals typed as HERC2 rs12913832 G. However, both methods had difficulties in categorizing individuals typed as HERC2 rs12913832 GA because of the large variation in eye colour in HERC2 rs12913832 GA individuals. With the use of the DIAT software and the PIE-score, it will be possible to automatically compare the iris colour of large numbers of iris images obtained by different studies and to perform large meta-studies that may reveal loci with small effects on the eye colour.