Evaluation of improved CT-based hardware attenuation correction in PET/MRI: Application to a 16-channel RF breast coil.

PURPOSE: The aim of this study was to compare and evaluate three different bilinear conversion curves for attenuation correction (AC) of a 16-channel radiofrequency (RF) coil in positron emission tomography/magnetic resonance (PET/MR) breast cancer imaging. METHODS: The quantitative impact of three different bilinear conversions of computed tomography (CT) data for the AC of a 16-channel RF breast coil was systematically evaluated in phantom measurements and on n = 20 PET/MR patients with breast cancer. PET data were reconstructed four times: (1) no coil AC (C-NAC) serving as a reference, (2) established bilinear conversion by Carney et al., (3) bilinear conversion by Paulus et al., and (4) bilinear conversion by Oehmigen et al. Relative differences in PET data were calculated. RESULTS: Independent of the choice of bilinear conversion, significant gains in PET signal, compared to C-NAC, were measurable in all phantom and patient measurements. Mean relative differences of ca. 10% in SUVmean (i.e., standardized uptake value; maximal relative differences up to 30%) due to the integration of the coil AC were calculated, compared to C-NAC in phantom and patient measurements. Relative difference images depict that the quantitative impact of coil AC is highest in regions close to the RF coil when compared to no AC data. Bilinear conversion by Carney et al. shows a slightly overcorrection (2.9%), whereas the conversion by Paulus et al. provides a slight undercorrection of the PET images (-1.6%) in comparison to the no-coil measurement. The bilinear conversion proposed by Oehmigen et al. provides the most appropriate AC for the breast coil in this phantom experiment (-0.2%). A total of 23 congruent lesions could be detected in all patients. All lesions could be detected in all reconstructions. CONCLUSIONS: For the best possible PET image quality and accurate PET quantification in breast PET/MRI, the AC of MR hardware components is important. The bilinear conversion proposed by Oehmigen et al. provides the most appropriate AC for the breast coil in this study.

CAD-based hardware attenuation correction in PET/MRI: First methodical investigations and clinical application of a 16-channel RF breast coil.

PURPOSE: Aim of this study was to evaluate the use of computer-aided design (CAD) models for attenuation correction (AC) of hardware components in positron emission tomography/magnetic resonance (PET/MR) imaging. METHODS: The technical feasibility and quantitative impact of CAD-AC compared to computer tomography (CT)-based AC (reference) was investigated on a modular phantom consisting of 19 different material samples (plastics and metals arranged around a cylindrical emission phantom) typically used in phantoms, patient tables, and radiofrequency (RF) coils in PET/MR. The clinical applicability of the CAD-AC method was then evaluated on a 16-channel RF breast coil in a PET/MR patient study. The RF breast coil in this study was specifically designed PET compatible. Using this RF breast coil, the impact on clinical PET/MR breast imaging was systematically evaluated in breast phantom measurements and, furthermore, in n = 10 PET/MR patients with breast cancer. PET data were reconstructed three times: (1) no AC (NAC), (2) established CT-AC, and (3) CAD-AC. For both phantom measurements, a scan without attenuating hardware components (material probes or RF breast coil) was acquired serving as reference. Relative differences in PET data were calculated for all experiments. RESULTS: In all phantom and patient measurements, significant gains in PET signal compared to NAC data were measurable with CT and CAD-AC. In initial phantom experiments, mean relative differences of -0.2% for CT-AC and 0.2% for CAD-AC were calculated compared to reference measurements without the material probes. The application to a RF breast coil depicts that CAD-AC results in significant gains compared to NAC data (10%) and a slight underestimation in PET signal of -1.3% in comparison to the no-coil reference measurement. In the patient study, a total of 15 congruent lesions in all 10 patients with a mean relative difference of 14% (CT and CAD-AC) in standardized uptake value compared to NAC data could be detected. CONCLUSIONS: To ensure best possible PET image quality and accurate PET quantification in PET/MR imaging, the AC of hardware components such as phantoms and RF coils is important. In initial phantom experiments and in clinical application to an RF breast coil, it was found that CAD-based AC results in significant gains in PET signal compared to NAC data and provides comparably good results to the established method of CT-based AC.

Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients.

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1-13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7-11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5-6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. SIGNIFICANCE: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7-11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.

Hyperpolarized 13C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer.

Purpose: To compare hyperpolarized carbon 13 (13C) MRI with dynamic contrast material-enhanced (DCE) MRI in the detection of early treatment response in breast cancer. Materials and Methods: In this institutional review board-approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent 13C MRI after injection of hyperpolarized [1-carbon 13 {13C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The 13C-labeled lactate-to-pyruvate ratio derived from hyperpolarized 13C MRI and the pharmacokinetic parameters transfer constant (K trans) and washout parameter (k ep) derived from DCE MRI were compared before and after treatment. Results: Exchange of the 13C label between injected hyperpolarized [1-13C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the 13C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean K trans (132%) and mean k ep (31%), which could be incorrectly interpreted as a poor response to treatment. Conclusion: Hyperpolarized 13C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI.Published under a CC BY 4.0 license.

Imaging breast cancer using hyperpolarized carbon-13 MRI.

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

Integrated PET/MR breast cancer imaging: Attenuation correction and implementation of a 16-channel RF coil.

PURPOSE: This study aims to develop, implement, and evaluate a 16-channel radiofrequency (RF) coil for integrated positron emission tomography/magnetic resonance (PET/MR) imaging of breast cancer. The RF coil is designed for optimized MR imaging performance and PET transparency and attenuation correction (AC) is applied for accurate PET quantification. METHODS: A 16-channel breast array RF coil was designed for integrated PET/MR hybrid imaging of breast cancer lesions. The RF coil features a lightweight rigid design and is positioned with a spacer at a defined position on the patient table of an integrated PET/MR system. Attenuation correction is performed by generating and applying a dedicated 3D CT-based template attenuation map. Reposition accuracy of the RF coil on the system patient table while using the positioning frame was tested in repeated measurements using MR-visible markers. The MR, PET, and PET/MR imaging performances were systematically evaluated using modular breast phantoms. Attenuation correction of the RF coil was evaluated with difference measurements of the active breast phantoms filled with radiotracer in the PET detector with and without the RF coil in place, serving as a standard of reference measurement. The overall PET/MR imaging performance and PET quantification accuracy of the new 16-channel RF coil and its AC were then evaluated in first clinical examinations on ten patients with local breast cancer. RESULTS: The RF breast array coil provides excellent signal-to-noise ratio and signal homogeneity across the volume of the breast phantoms in MR imaging and visualizes small structures in the phantoms down to 0.4 mm in plane. Difference measurements with PET revealed a global loss and thus attenuation of counts by 13% (mean value across the whole phantom volume) when the RF coil is placed in the PET detector. Local attenuation ranging from 0% in the middle of the phantoms up to 24% was detected in the peripheral regions of the phantoms at positions closer to attenuating hardware structures of the RF coil. The position accuracy of the RF coil on the patient table when using the positioning frame was determined well below 1 mm for all three spatial dimensions. This ensures perfect position match between the RF coil and its three-dimensional attenuation template during the PET data reconstruction process. When applying the CT-based AC of the RF coil, the global attenuation bias was mostly compensated to ±0.5% across the entire breast imaging volume. The patient study revealed high quality MR, PET, and combined PET/MR imaging of breast cancer. Quantitative activity measurements in all 11 breast cancer lesions of the ten patients resulted in increased mean difference values of SUVmax 11.8% (minimum 3.2%; maximum 23.2%) between nonAC images and images when AC of the RF breast coil was applied. This supports the quantitative results of the phantom study as well as successful attenuation correction of the RF coil. CONCLUSIONS: A 16-channel breast RF coil was designed for optimized MR imaging performance and PET transparency and was successfully integrated with its dedicated attenuation correction template into a whole-body PET/MR system. Systematic PET/MR imaging evaluation with phantoms and an initial study on patients with breast cancer provided excellent MR and PET image quality and accurate PET quantification.

A 16-channel MR coil for simultaneous PET/MR imaging in breast cancer.

OBJECTIVES: To implement and evaluate a dedicated receiver array coil for simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging in breast cancer. METHODS: A 16-channel receiver coil design was optimized for simultaneous PET/MR imaging. To assess MR performance, the signal-to-noise ratio, parallel imaging capability and image quality was evaluated in phantoms, volunteers and patients and compared to clinical standard protocols. For PET evaluation, quantitative (18) F-FDG PET images of phantoms and seven patients (14 lesions) were compared to images without the coil. In PET image reconstruction, a CT-based template of the coil was combined with the MR-acquired attenuation correction (AC) map of the phantom/patient. RESULTS: MR image quality was comparable to clinical MR-only examinations. PET evaluation in phantoms showed regionally varying underestimation of the standardised uptake value (SUV; mean 22 %) due to attenuation caused by the coil. This was improved by implementing the CT-based coil template in the AC (<2 % SUV underestimation). Patient data indicated that including the coil in the AC increased the SUV values in the lesions (21 ± 9 %). CONCLUSIONS: Using a dedicated PET/MR breast coil, state-of-the-art MRI was possible. In PET, accurate quantification and image homogeneity could be achieved if a CT-template of this coil was included in the AC for PET image reconstruction. KEY POINTS: • State-of-the-art breast MRI using a dedicated PET/MR breast coil is feasible. • A multi-channel design facilitates shorter MR acquisition times via parallel imaging. • An MR coil inside a simultaneous PET/MR system causes PET photon attenuation. • Including a coil CT-template in PET image reconstruction results in recovering accurate quantification.

Comprehensive small animal imaging strategies on a clinical 3 T dedicated head MR-scanner; adapted methods and sequence protocols in CNS pathologies.

BACKGROUND: Small animal models of human diseases are an indispensable aspect of pre-clinical research. Being dynamic, most pathologies demand extensive longitudinal monitoring to understand disease mechanisms, drug efficacy and side effects. These considerations often demand the concomitant development of monitoring systems with sufficient temporal and spatial resolution. METHODOLOGY AND RESULTS: This study attempts to configure and optimize a clinical 3 Tesla magnetic resonance scanner to facilitate imaging of small animal central nervous system pathologies. The hardware of the scanner was complemented by a custom-built, 4-channel phased array coil system. Extensive modification of standard sequence protocols was carried out based on tissue relaxometric calculations. Proton density differences between the gray and white matter of the rodent spinal cord along with transverse relaxation due to magnetic susceptibility differences at the cortex and striatum of both rats and mice demonstrated statistically significant differences. The employed parallel imaging reconstruction algorithms had distinct properties dependent on the sequence type and in the presence of the contrast agent. The attempt to morphologically phenotype a normal healthy rat brain in multiple planes delineated a number of anatomical regions, and all the clinically relevant sequels following acute cerebral ischemia could be adequately characterized. Changes in blood-brain-barrier permeability following ischemia-reperfusion were also apparent at a later time. Typical characteristics of intra-cerebral haemorrhage at acute and chronic stages were also visualized up to one month. Two models of rodent spinal cord injury were adequately characterized and closely mimicked the results of histological studies. In the employed rodent animal handling system a mouse model of glioblastoma was also studied with unequivocal results. CONCLUSIONS: The implemented customizations including extensive sequence protocol modifications resulted in images of high diagnostic quality. These results prove that lack of dedicated animal scanners shouldn't discourage conventional small animal imaging studies.

Real-time 3D MRI of contrast agents in whole living mice.

A specific mouse whole body coil and a dedicated gradient system at 4.7 T were coupled with an ultra-fast 3D gradient echo MRI and keyhole reconstruction technique to obtain 3D whole-body dynamic T(1)-weighted or T(2)*-weighted imaging. The technique was used to visualize the real-time distribution of non-targeting T(1) and T(2)* contrast agent (CA) in a glioma-bearing mouse model. T(1) dynamic contrast-enhancement imaging was performed with a fast imaging with steady-state precession sequence [echo time/repetition time (TE/TR), 1.32/3.7 ms] before and after CA injection (Gd-DOTA and BSA-Gd-DOTA) for 21 min. The temporal resolution was 1 image/6.5 s. T(2)* imaging (TE/TR, 4/8 ms) was performed before and after iron-based (small and ultra-small particles of iron oxide) CA injection for 45 min. The temporal resolution was 1 image/14 s. Signal-to-noise ratio curves were determined in various mouse organs. The whole-body coil and gradient systems made it possible to acquire data with sufficient and homogeneous signal-to-noise ratio on the whole animal. The spatial resolution allowed adequate depiction of the major organs, blood vessels and brain glioma. The distribution and the time-course of T(1) and T(2)* contrasts upon contrast agent injection were also assessed. 3D whole-body mouse MRI is feasible at high spatial resolution in movie mode and can be applied successfully to visualize real-time contrast agent distribution. This method should be effective in future preclinical molecular imaging studies.

Brain tumor enhancement in magnetic resonance imaging at 3 tesla: intraindividual comparison of two high relaxivity macromolecular contrast media with a standard extracellular gd-chelate in a rat brain tumor model.

OBJECTIVES: The aim of this study was to evaluate lesion enhancement (LE) and contrast-to-noise ratio (CNR) properties of P846, a new intermediate sized, high relaxivity Gd-based contrast agent at 3 Tesla in a rat brain glioma model, and to compare this contrast agent with a high relaxivity, macromolecular compound (P792), and a standard extracellular Gd-chelate (Gd-DOTA). MATERIALS AND METHODS: Seven rats with experimental induced brain glioma were evaluated using 3 different contrast agents, with each MR examination separated by at least 24 hours. The time between injections assured sufficient clearance of the agent from the tumor, before the next examination. P792 (Gadomelitol, Guerbet, France) and P846 (a new compound from Guerbet Research) are macromolecular and high relaxivity contrast agents with no protein binding, and were compared with the extracellular agent Gd-DOTA (Dotarem, Guerbet, France). T1w gradient echo sequences (TR/TE 200 milliseconds/7.38 milliseconds, flip angle = 90 degrees , acquisition time: 1:42 minutes:sec, voxel size: 0.2 x 0.2 x 2.0 mm, FOV = 40 mm, acquisition matrix: 256 x 256) were acquired before and at 5 consecutive time points after each intravenous contrast injection in the identical slice orientation, using a dedicated 4-channel head array animal coil. The order of contrast media injection was randomized, with however Gd-DOTA used either as the first or second contrast agent. Contrast agent dose was adjusted to compensate for the different T1 relaxivities of the 3 agents. Signal-to-noise ratio, CNR, and LE were evaluated using region-of-interest analysis. A veterinary histopathologist confirmed the presence of a glioma in each subject, after completion of the imaging study. RESULTS: P792 showed significantly less LE as compared with Gd-DOTA within the first 7 minutes after contrast agent injection (P < 0.05) with, however, reaching comparable LE values at 9 minutes after injection (P = 0.07). However, P792 provided significantly less CNR as compared with Gd-DOTA (P < 0.05) for all examination time points. P846 provided comparable but persistent LE as compared with Gd-DOTA (P < 0.05) and demonstrated significantly greater LE and CNR when compared with P792 (P < 0.05). No statistically significant differences between CNR values for Gd-DOTA and P846 were noted for all examination time points (P < 0.05), with P846 administered at one-fourth the dose as compared with Gd-DOTA. CONCLUSION: The intravascular contrast medium P792 showed significantly less LE and CNR in comparison to Gd-DOTA and P846, suggesting that it does not show marked extravasation from tumor neocapillaries and does not significantly cross the disrupted blood brain-barrier in this rat glioma model. In distinction, P846 provides comparable enhancement properties at a field strength of 3 Tesla to the extracellular contrast agent Gd-DOTA, using the adjusted dose, suggesting that it crosses the disrupted blood-brain-barrier and tumor capillaries, most likely based on the decreased molecular weight as compared with P792. At the same time, the high relaxivity of this compound allows for decreasing the injected gadolinium dose by a factor of 4 whereas providing comparable enhancement properties when compared with a standard extracellular Gd-chelate (Gd-DOTA) at a dose of 0.1 mmol/kg body weight.