Age-associated change in pyruvate metabolism investigated with hyperpolarized 13 C-MRI of the human brain.

In this study, hyperpolarized 13 C MRI (HP-13 C MRI) was used to investigate changes in the uptake and metabolism of pyruvate with age. Hyperpolarized 13 C-pyruvate was administered to healthy aging individuals (N = 35, ages 21-77) and whole-brain spatial distributions of 13 C-lactate and 13 C-bicarbonate production were measured. Linear mixed-effects regressions were performed to compute the regional percentage change per decade, showing a significant reduction in both normalized 13 C-lactate and normalized 13 C-bicarbonate production with age: - 7 % ± 2 % per decade for 13 C-lactate and - 9 % ± 4 % per decade for 13 C-bicarbonate. Certain regions, such as the right medial precentral gyrus, showed greater rates of change while the left caudate nucleus had a flat 13 C-lactate versus age and a slightly increasing 13 C-bicarbonate versus age. The results show that both the production of lactate (visible as 13 C-lactate signal) as well as the consumption of monocarboxylates to make acetyl-CoA (visible as 13 C-bicarbonate signal) decrease with age and that the rate of change varies by brain region.

Catheter reconstruction and dosimetric verification of MRI-only treatment planning (MRTP) for interstitial HDR brachytherapy using PETRA sequence.

Objective. The feasibility of MRI-only treatment planning (MRTP) for interstitial high-dose rate (HDR) brachytherapy (BT) was investigated for patients diagnosed with gynecologic cancer.Approach. A clinical MRTP workflow utilizing a 'pointwise encoding time reduction with radial acquisition (PETRA)' sequence was proposed. This is a clinically available MRI sequence optimized to improve interstitial catheter-tissue contrast. Interstitial needles outside the obturator region were reconstructed using MR images only. For catheters penetrating through the obturator, a library-based reconstruction was proposed. In this work, dwell coordinates from the clinical CT-based reconstruction were used as the surrogate for the library-based approach. For MR-only plan, dwell times were activated and assigned as in the clinical plans. The catheter reconstruction was assessed by comparing dwell position coordinates. The dosimetric comparisons between a clinical plan and MR-only plan were assessed for physical and EQD2 dose and volume parameters forD90,D50andD98for clinical target volume (CTV) andD2cc,D0.1ccandD5ccfor OARs.Main results. Catheter reconstruction was possible using the optimized PETRA sequence on MR images. An overall reconstruction difference of 1.7 ± 0.5 mm, attributed to registration-based errors, was found compared to the CT-based reconstruction. The MRTP workflow has the potential to generate a treatment plan with an equivalent dosimetric quality compared to the conventional CT/MRI-based approach. For CTVD90, physical and EQD2 dose and volume parameter differences were 1.5 ± 1.9% and 0.7 ± 1.0 Gy, respectively. ForD2ccOARs, DVH (EQD2) differences were -0.4 ± 1.1% (-0.2 ± 0.5 Gy), 0.5 ± 2.8% (0.2 ± 1.3 Gy) and -0.5 ± 1.4% (-0.2 ± 0.5 Gy) for rectum, bladder, and sigmoid, respectively.Significance. With the proposed MRTP approach, CT imaging may no longer be needed in HDR BT for interstitial gynecologic treatment. A proof-of-concept study was conducted to demonstrated that MRTP using PETRA is feasible, with comparable dosimetric results to the conventional CT/MRI-based approach.

First pointwise encoding time reduction with radial acquisition (PETRA) implementation for catheter detection in interstitial high-dose-rate (HDR) brachytherapy.

PURPOSE: A pointwise encoding time reduction with radial acquisition (PETRA) sequence was optimized to detect empty catheters in interstitial (HDR) brachytherapy with clinically acceptable spatial accuracy for the first time. Image quality and catheter detectability were assessed in phantoms, and the feasibility of PETRA's clinical implementation was assessed on a gynecological cancer patient. METHODS AND RESULTS: Empty catheters embedded in a gelatin phantom displayed positive signal on PETRA and more accurate cross-sections than on clinically employed T2-weighted sequences, differing by 0.4 mm on average from their nominal 2 mm diameter. PETRA presented minimal susceptibility differences and a symmetric metal artifact, contrary to the clinical sequences. The PETRA-CT catheter tip position differences assessed by a treatment planning system (TPS) were < 1 mm. PETRA also detected an interstitial template with empty catheters penetrating a poultry phantom and fused very well with CT. Interstitial catheter positional difference between PETRA and CT images was < 1 mm on average, increasing with distance from isocenter. All interstitial catheters and the employed interstitial template were detected on PETRA images of an endometrial adenocarcinoma patient. Empty needles were traceable using a TPS, with higher spatial resolution and more favorable contrast than on T2-weighted images used for contouring. A treatment plan could be produced by combining information from PETRA for catheter detection and from T2-weighted images for tumor and organs delineation. CONCLUSIONS: PETRA detected successfully and accurately interstitial catheters in phantoms. Its first clinical implementation shows a potential for MR-only treatment planning in interstitial HDR brachytherapy.

Feasibility of magnetic resonance-only high-dose-rate surface brachytherapy for clinical application.

PURPOSE: In this article, we investigate the feasibility of magnetic resonance (MR)-only imaging for high-dose-rate (HDR) surface brachytherapy (SABT). We examined whether a standard CT-based planning can be replaced with an MR-only planning. For this purpose, the MRI digitization and plan quality check processes were compared against the standard CT-based processes. A prospective clinical implementation of the MR-only planning was evaluated on a clinical data set. METHODS: A pointwise encoding time reduction with radial acquisition (PETRA) sequence was optimized for visualization of Freiburg flap (FF) on MR images. MR and conventional CT images were acquired with a FF applicator (Elekta, Stockholm, Sweden) placed on the following phantoms: (1) flat styrofoam (FST), FF locked-in placed with supporting structure; (2) cast-made facemask, and (3) porcine leg (PL). Catheters were digitized and activated with 10 mm step size on Oncentra Brachy 4.5.3 Treatment Planning System. The CT-only and MR-only treatment plans were generated by optimizing the dose to the target defined as volume at 3 mm skin depth. To compare the plans, the MRI-to-CT alignment was performed via rigid registration. Positional displacements of dwell positions between CT and MR plans were compared on the FST phantom and the relative percent dose difference in 2210 different points from CT or MR-only plans was compared. For all three phantoms, the comparabilities between CT and MR-only plans were assessed by calculating dice similarity coefficient (DSC) for volumes enclosing 150%, 125%, 100%, 95%, 90%, 80%, and 65% isodose lines (V150  -V65 ). The MR images of FF placed on the forearm of a healthy subject were acquired with this optimized PETRA sequence and used for treatment planning. The relative percent dose was calculated on 140 representative points placed at 3 mm skin depth to evaluate the dose to the skin. RESULTS: Using the optimized PETRA sequence, MRTP digitization accuracy was < 1 mm in each dimension and on three-dimensional (3D) displacement for the FST phantom. In each phantom and clinical data set, it was possible to generate MR-only treatment plans with the 3 mm skin depth prescription. In the FST phantom, the mean relative dose at the points was not significantly different (< 0.1% difference) for CT or MR-based plans. The assessment of similarities in dose profiles between CT and MR-only plans' provided DSC values greater than 0.96, 0.92, and 0.73 for all volumes enclosing up to 100%, 125%, and 150% isodose lines, respectively. CONCLUSION: The feasibility of generating a HDR treatment plan with FF using MR-only has been evaluated in phantoms with varying geometry and for a clinical data set. The optimization of a standard MRI sequence-PETRA-implemented in this study showed that FF-based catheters can be digitized and a plan can be generated using only MRI. The resulting MR-only plans were comparable to the conventional CT-based plans, suggesting that MRI alone can generate clinically acceptable plans for FF in phantoms and on a clinical data set. Reliable MR-only treatment planning could improve treatment prescription through more accurate characterization of soft tissue targets.

Predicting response to radiotherapy of intracranial metastases with hyperpolarized [Formula: see text]C MRI.

BACKGROUND: Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume of enhancement on serial MRI scans which may lag true progression by weeks or months. METHODS: Patients with intracranial metastases (N = 11) were scanned using hyperpolarized [Formula: see text]C MRI prior to treatment with stereotactic radiosurgery (SRS). The status of each lesion was then recorded at six months post-treatment follow-up (or at the time of death). RESULTS: The positive predictive value of [Formula: see text]C-lactate signal, measured pre-treatment, for prediction of progression of intracranial metastases at six months post-treatment with SRS was 0.8 [Formula: see text], and the AUC from an ROC analysis was 0.77 [Formula: see text]. The distribution of [Formula: see text]C-lactate z-scores was different for intracranial metastases from different primary cancer types (F = 2.46, [Formula: see text]). CONCLUSIONS: Hyperpolarized [Formula: see text]C imaging has potential as a method for improving outcomes for patients with intracranial metastases, by identifying patients at high risk of treatment failure with SRS and considering other therapeutic options such as surgery.

Correlation of hyperpolarized 13 C-MRI data with tissue extract measurements.

Hyperpolarized (HP) 13C MRI provides the means to monitor lactate metabolism noninvasively in tumours. Since 13C -lactate signal levels obtained from HP 13C imaging depend on multiple factors, such as the rate of 13C substrate delivery via the vasculature, the expression level of monocarboxylate transporters (MCTs) and lactate dehydrogenase (LDH), and the local lactate pool size, the interpretation of HP 13C metabolic images remains challenging. In this study, ex vivo tissue extract measurements (i.e., NMR isotopomer analysis, western blot analysis) derived from an MDA-MB-231 xenograft model in nude rats were used to test for correlations between the in vivo 13C data and the ex vivo measures. The lactate-to-pyruvate ratio from HP 13C MRI was strongly correlated with [1- 13C ]lactate concentration measured from the extracts using NMR (R = 0.69, p < 0.05), as well as negatively correlated with tumour wet weight (R = -  0.60, p < 0.05). In this tumour model, both MCT1 and MCT4 expressions were positively correlated with wet weight ( ρ = 0.78 and 0.93, respectively, p < 0.01). Lactate pool size and the lactate-to-pyruvate ratio were not significantly correlated.

Lactate topography of the human brain using hyperpolarized 13C-MRI.

Lactate is now recognized as an important intermediate in brain metabolism, but its role is still under investigation. In this work we mapped the distribution of lactate and bicarbonate produced from intravenously injected 13C-pyruvate over the whole brain using a new imaging method, hyperpolarized 13C MRI (N = 14, ages 23 to 77). Segmenting the 13C-lactate images into brain atlas regions revealed a pattern of lactate that was preserved across individuals. Higher lactate signal was observed in cortical grey matter compared to white matter and was highest in the precuneus, cuneus and lingual gyrus. Bicarbonate signal, indicating flux of [1-13C]pyruvate into the TCA cycle, also displayed consistent spatial distribution. One-way ANOVA to test for significant differences in lactate among atlas regions gave F = 87.6 and p < 10-6. This report of a "lactate topography" in the human brain and its consistent pattern is evidence of region-specific lactate biology that is preserved across individuals.

Partial Fourier reconstruction for improved resolution in 3D hyperpolarized 13 C EPI.

PURPOSE: Asymmetric in-plane k-space sampling of EPI can reduce the minimum achievable TE in hyperpolarized 13C with spectral-spatial radio frequency pulses, thereby reducing T2* weighting and signal-losses. Partial Fourier image reconstruction exploits the approximate Hermitian symmetry of k-space data and can be applied to asymmetric data sets to synthesize unmeasured data. Here we tested whether the application of partial Fourier image reconstruction would improve spatial resolution from hyperpolarized [1- 13C ]pyruvate scans in the human brain. METHODS: Fifteen healthy control subjects were imaged using a volumetric dual-echo echo-planar imaging sequence with spectral-spatial radio frequency excitation. Images were reconstructed by zero-filling as well as with the partial Fourier reconstruction algorithm projection-on-convex-sets. Resulting images were quantitatively evaluated with a no-reference image quality assessment. RESULTS: The no-reference image sharpness metric agreed with perceived improvements in image resolution and contrast. The [1- 13C ]lactate images benefitted most, followed by the [1- 13C ]pyruvate images. The 13C -bicarbonate images were improved by the smallest degree, likely owing to relatively lower SNR. CONCLUSIONS: Partial Fourier imaging and reconstruction were shown to improve the sharpness and contrast of human HP 13C brain data and is a viable method for enhancing resolution.

Investigating the Relationship between Transverse Relaxation Rate (R2) and Interecho Time in MagA-Expressing, Iron-Labeled Cells.

Reporter gene-based labeling of cells with iron is an emerging method of providing magnetic resonance imaging contrast for long-term cell tracking and monitoring cellular activities. This report investigates 9.4 T nuclear magnetic resonance properties of mammalian cells overexpressing MagA, a putative iron transport protein from magnetotactic bacteria. MagA-expressing MDA-MB-435 cells were cultured in the presence and absence of iron supplementation and compared to the untransfected control. The relationship between the transverse relaxation rate (R2) and interecho time was investigated using the Carr-Purcell-Meiboom-Gill sequence. This relationship was analyzed using a model based on water diffusion in weak magnetic field inhomogeneities (Jensen-Chandra model) as well as a fast-exchange model (Luz-Meiboom model). Increases in R2 with increasing interecho time were larger in the iron-supplemented, MagA-expressing cells compared to other cells. The dependence of R2 on interecho time in these iron-supplemented, MagA-expressing cells was better represented by the Jensen-Chandra model compared to the Luz-Meiboom model, whereas the Luz-Meiboom model performed better for the remaining cell types. Our findings provide an estimate of the distance scale of microscopic magnetic field variations in MagA-expressing cells, which is thought to be related to the size of iron-containing vesicles.