Purpose
Accurate glioma classification affects patient management and is challenging on non- or low-enhancing gliomas. This study investigated the clinical value of different chemical exchange ...saturation transfer (CEST) metrics for glioma classification and assessed the diagnostic effect of the presence of abundant fluid in glioma subpopulations.
Methods
Forty-five treatment-naïve glioma patients with known isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status received CEST MRI (
B
1rms
= 2μT,
T
sat
= 3.5 s) at 3 T. Magnetization transfer ratio asymmetry and CEST metrics (amides: offset range 3–4 ppm, amines: 1.5–2.5 ppm, amide/amine ratio) were calculated with two models: ‘asymmetry-based’ (AB) and ‘fluid-suppressed’ (FS). The presence of T2/FLAIR mismatch was noted.
Results
IDH-wild type had higher amide/amine ratio than IDH-mutant_1p/19q
codel
(
p
< 0.022). Amide/amine ratio and amine levels differentiated IDH-wild type from IDH-mutant (
p
< 0.0045) and from IDH-mutant_1p/19q
ret
(
p
< 0.021). IDH-mutant_1p/19q
ret
had higher amides and amines than IDH-mutant_1p/19q
codel
(
p
< 0.035). IDH-mutant_1p/19q
ret
with AB/FS mismatch had higher amines than IDH-mutant_1p/19q
ret
without AB/FS mismatch ( < 0.016). In IDH-mutant_1p/19q
ret
, the presence of AB/FS mismatch was closely related to the presence of T2/FLAIR mismatch (
p
= 0.014).
Conclusions
CEST-derived biomarkers for amides, amines, and their ratio can help with histomolecular staging in gliomas without intense contrast enhancement. T2/FLAIR mismatch is reflected in the presence of AB/FS CEST mismatch. The AB/FS CEST mismatch identifies glioma subgroups that may have prognostic and clinical relevance.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Tumors have a greater reliance on anaerobic glycolysis for energy production than normal tissues. We developed a noninvasive method for imaging glucose uptake in vivo that is based on magnetic ...resonance imaging and allows the uptake of unlabeled glucose to be measured through the chemical exchange of protons between hydroxyl groups and water. This method differs from existing molecular imaging methods because it permits detection of the delivery and uptake of a metabolically active compound in physiological quantities. We show that our technique, named glucose chemical exchange saturation transfer (glucoCEST), is sensitive to tumor glucose accumulation in colorectal tumor models and can distinguish tumor types with differing metabolic characteristics and pathophysiologies. The results of this study suggest that glucoCEST has potential as a useful and cost-effective method for characterizing disease and assessing response to therapy in the clinic.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Increased extracellular sodium activates Th17 cells, which provide protection from bacterial and fungal infections. Whilst high salt diets have been shown to worsen autoimmune disease, the ...immunological consequences of clinical salt depletion are unknown. Here, we investigate immunity in patients with inherited salt-losing tubulopathies (SLT). Forty-seven genotyped SLT patients (with Bartter, Gitelman or EAST Syndromes) are recruited. Clinical features of dysregulated immunity are recorded with a standardised questionnaire and immunological investigations of IL-17 responsiveness undertaken. The effects of altering extracellular ionic concentrations on immune responses are then assessed. Patients are hypokalaemic and hypomagnesaemic, with reduced interstitial sodium stores determined by
23
Na-magnetic resonance imaging. SLT patients report increased mucosal infections and allergic disease compared to age-matched controls. Aligned with their clinical phenotype, SLT patients have an increased ratio of Th2:Th17 cells. SLT Th17 and Tc17 polarisation is reduced in vitro, yet STAT1 and STAT3 phosphorylation and calcium flux following T cell activation are unaffected. In control cells, the addition of extracellular sodium (+40 mM), potassium (+2 mM), or magnesium (+1 mM) reduces Th2:Th17 ratio and augments Th17 polarisation. Our results thus show that the ionic environment typical in SLT impairs IL-17 immunity, but the intracellular pathways that mediate salt-driven Th17 polarisation are intact and in vitro IL-17 responses can be reinvigorated by increasing extracellular sodium concentration. Whether better correction of extracellular ions can rescue the immunophenotype in vivo in SLT patients remains unknown.
23Na MRI can be used to quantify in-vivo tissue sodium concentration (TSC), but the inherently low 23Na signal leads to long scan times and/or noisy or low-resolution images. Reconstruction ...algorithms such as compressed sensing (CS) have been proposed to mitigate low signal-to-noise ratio (SNR); although, these can result in unnatural images, suboptimal denoising and long processing times. Recently, machine learning has been increasingly used to denoise 1H MRI acquisitions; however, this approach typically requires large volumes of high-quality training data, which is not readily available for 23Na MRI. Here, we propose using 1H data to train a denoising convolutional neural network (CNN), which we subsequently demonstrate on prospective 23Na images of the calf.
1893 1H fat-saturated transverse slices of the knee from the open-source fastMRI dataset were used to train denoising CNNs for different levels of noise. Synthetic low SNR images were generated by adding gaussian noise to the high-quality 1H k-space data before reconstruction to create paired training data. For prospective testing, 23Na images of the calf were acquired in 10 healthy volunteers with a total of 150 averages over ten minutes, which were used as a reference throughout the study. From this data, images with fewer averages were retrospectively reconstructed using a non-uniform fast Fourier transform (NUFFT) as well as CS, with the NUFFT images subsequently denoised using the trained CNN.
CNNs were successfully applied to 23Na images reconstructed with 50, 40 and 30 averages. Muscle and skin apparent TSC quantification from CNN-denoised images were equivalent to those from CS images, with <0.9 mM bias compared to reference values. Estimated SNR was significantly higher in CNN-denoised images compared to NUFFT, CS and reference images. Quantitative edge sharpness was equivalent for all images. For subjective image quality ranking, CNN-denoised images ranked equally best with reference images and significantly better than NUFFT and CS images.
Denoising CNNs trained on 1H data can be successfully applied to 23Na images of the calf; thus, allowing scan time to be reduced from ten minutes to two minutes with little impact on image quality or apparent TSC quantification accuracy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Na MRI can be used to quantify in-vivo tissue sodium concentration (TSC), but the inherently low
Na signal leads to long scan times and/or noisy or low-resolution images. Reconstruction algorithms ...such as compressed sensing (CS) have been proposed to mitigate low signal-to-noise ratio (SNR); although, these can result in unnatural images, suboptimal denoising and long processing times. Recently, machine learning has been increasingly used to denoise
H MRI acquisitions; however, this approach typically requires large volumes of high-quality training data, which is not readily available for
Na MRI. Here, we propose using
H data to train a denoising convolutional neural network (CNN), which we subsequently demonstrate on prospective
Na images of the calf.
1893
H fat-saturated transverse slices of the knee from the open-source fastMRI dataset were used to train denoising CNNs for different levels of noise. Synthetic low SNR images were generated by adding gaussian noise to the high-quality
H k-space data before reconstruction to create paired training data. For prospective testing,
Na images of the calf were acquired in 10 healthy volunteers with a total of 150 averages over ten minutes, which were used as a reference throughout the study. From this data, images with fewer averages were retrospectively reconstructed using a non-uniform fast Fourier transform (NUFFT) as well as CS, with the NUFFT images subsequently denoised using the trained CNN.
CNNs were successfully applied to
Na images reconstructed with 50, 40 and 30 averages. Muscle and skin apparent TSC quantification from CNN-denoised images were equivalent to those from CS images, with <0.9 mM bias compared to reference values. Estimated SNR was significantly higher in CNN-denoised images compared to NUFFT, CS and reference images. Quantitative edge sharpness was equivalent for all images. For subjective image quality ranking, CNN-denoised images ranked equally best with reference images and significantly better than NUFFT and CS images.
Denoising CNNs trained on
H data can be successfully applied to
Na images of the calf; thus, allowing scan time to be reduced from ten minutes to two minutes with little impact on image quality or apparent TSC quantification accuracy.
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Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Chemical exchange saturation transfer (CEST) can potentially support cancer imaging with metabolically derived information. Multiparametric prostate MRI has improved diagnosis but may ...benefit from additional information to reduce the need for biopsies.
Purpose
To optimize an acquisition and postprocessing protocol for 3.0 T multipool CEST analysis of prostate data and evaluate the repeatability of the technique.
Study Type
Prospective.
Subjects
Five healthy volunteers (age range: 24–47 years; median age: 28 years) underwent two sessions (interval range: 7–27 days; median interval: 20 days) and two biopsy‐proven prostate cancer patients were evaluated once. Patient 1 (71 years) had a Gleason 3 + 4 transition zone (TZ) tumor and patient 2 (55 years) had a Gleason 4 + 3 peripheral zone (PZ) tumor.
Field Strength
3.0 T. Sequences run: T2‐weighted turbo‐spin‐echo (TSE); diffusion‐weighted imaging; CEST; WASABI (for B0 determination).
Assessment
Saturation, readout, and fit‐model parameters were optimized to maximize in vivo amide and nuclear Overhauser effect (NOE) signals. Repeatability (intrasession and intersession) was evaluated in healthy volunteers. Subsequently, preliminary evaluation of signal differences was made in patients. Regions of interest were drawn by two post‐FRCR board‐certified readers, both with over 5 years of experience in multiparametric prostate MRI.
Statistical Tests
Repeatability was assessed using Bland–Altman analysis, coefficient of variation (CV), and 95% limits of agreement (LOA). Statistical significance of CEST contrast was calculated using a nonparametric Mann–Whitney U‐test.
Results
The optimized saturation scheme was found to be 60 sinc‐Gaussian pulses with 40 msec pulse duration, at 50% duty‐cycle with continuous‐wave pulse equivalent B1 power (B1CWPE) of 0.92 μT. The magnetization transfer (MT) contribution to the fit‐model was centered at –1.27 ppm. Intersession coefficients of variation (CVs) of the amide, NOE, and magnetization transfer (MT) and asymmetric magnetization transfer ratio (MTRasym) signals of 25%, 23%, 18%, and 200%, respectively, were observed. Fit‐metric and MTRasym CVs agreed between readers to within 4 and 10 percentage points, respectively.
Data Conclusion
Signal differences of 0.03–0.10 (17–43%) detectable depending upon pool, with MT the most repeatable (signal difference of 17–22% detectable).
Level of Evidence: 2
Technical Efficacy: Stage 2
J. Magn. Reson. Imaging 2019;50:1238–1250.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Sodium MRI can be used to quantify tissue sodium concentration (TSC) in vivo; however, UTE sequences are required to capture the rapidly decaying signal. 2D MRI enables high in-plane resolution but ...typically has long TEs. Half-sinc excitation may enable UTE; however, twice as many readouts are necessary. Scan time can be minimized by reducing the number of signal averages (NSAs), but at a cost to SNR. We propose using compressed sensing (CS) to accelerate 2D half-sinc acquisitions while maintaining SNR and TSC.
Ex vivo and in vivo TSC were compared between 2D spiral sequences with full-sinc (TE = 0.73 ms, scan time ≈ 5 min) and half-sinc excitation (TE = 0.23 ms, scan time ≈ 10 min), with 150 NSAs. Ex vivo, these were compared to a reference 3D sequence (TE = 0.22 ms, scan time ≈ 24 min). To investigate shortening 2D scan times, half-sinc data was retrospectively reconstructed with fewer NSAs, comparing a nonuniform fast Fourier transform to CS. Resultant TSC and image quality were compared to reference 150 NSAs nonuniform fast Fourier transform images.
TSC was significantly higher from half-sinc than from full-sinc acquisitions, ex vivo and in vivo. Ex vivo, half-sinc data more closely matched the reference 3D sequence, indicating improved accuracy. In silico modeling confirmed this was due to shorter TEs minimizing bias caused by relaxation differences between phantoms and tissue. CS was successfully applied to in vivo, half-sinc data, maintaining TSC and image quality (estimated SNR, edge sharpness, and qualitative metrics) with ≥50 NSAs.
2D sodium MRI with half-sinc excitation and CS was validated, enabling TSC quantification with 2.25 × 2.25 mm
resolution and scan times of ≤5 mins.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
BackgroundChemical exchange saturation transfer (CEST) can potentially support cancer imaging with metabolically derived information. Multiparametric prostate MRI has improved diagnosis but may ...benefit from additional information to reduce the need for biopsies.PurposeTo optimize an acquisition and postprocessing protocol for 3.0 T multipool CEST analysis of prostate data and evaluate the repeatability of the technique.Study TypeProspective.SubjectsFive healthy volunteers (age range: 24–47 years; median age: 28 years) underwent two sessions (interval range: 7–27 days; median interval: 20 days) and two biopsy‐proven prostate cancer patients were evaluated once. Patient 1 (71 years) had a Gleason 3 + 4 transition zone (TZ) tumor and patient 2 (55 years) had a Gleason 4 + 3 peripheral zone (PZ) tumor.Field Strength3.0 T. Sequences run: T2‐weighted turbo‐spin‐echo (TSE); diffusion‐weighted imaging; CEST; WASABI (for B0 determination).AssessmentSaturation, readout, and fit‐model parameters were optimized to maximize in vivo amide and nuclear Overhauser effect (NOE) signals. Repeatability (intrasession and intersession) was evaluated in healthy volunteers. Subsequently, preliminary evaluation of signal differences was made in patients. Regions of interest were drawn by two post‐FRCR board‐certified readers, both with over 5 years of experience in multiparametric prostate MRI.Statistical TestsRepeatability was assessed using Bland–Altman analysis, coefficient of variation (CV), and 95% limits of agreement (LOA). Statistical significance of CEST contrast was calculated using a nonparametric Mann–Whitney U‐test.ResultsThe optimized saturation scheme was found to be 60 sinc‐Gaussian pulses with 40 msec pulse duration, at 50% duty‐cycle with continuous‐wave pulse equivalent B1 power (B1CWPE) of 0.92 μT. The magnetization transfer (MT) contribution to the fit‐model was centered at –1.27 ppm. Intersession coefficients of variation (CVs) of the amide, NOE, and magnetization transfer (MT) and asymmetric magnetization transfer ratio (MTRasym) signals of 25%, 23%, 18%, and 200%, respectively, were observed. Fit‐metric and MTRasym CVs agreed between readers to within 4 and 10 percentage points, respectively.Data ConclusionSignal differences of 0.03–0.10 (17–43%) detectable depending upon pool, with MT the most repeatable (signal difference of 17–22% detectable).Level of Evidence: 2Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;50:1238–1250.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
We assessed DOPA PET for staging (5) or progression (10) in adolescent patients (age 17 ± 4) with brain tumour in comparison with contrast MRI. 15 patients underwent 18 DOPA PET/MRI (2 had ...repeated follow up) (2 germinoma and 13 gliomas, 7 high grade HGG and 6 low grade gliomaLGG). Two NM physicians recorded quantitative PET parameters. Two neuroradiologists recorded tumour characteristics. The Gold Standard was either surgery or clinical follow-up. The readers drew the volume of tumour on a dedicated platform (ITK-SNAP) on PET or on MR. The association of PET and MRI parameters was evaluated by non-parametric correlation analysis. Intermodality variability on the PET and MRI volumes, their ratios and percentage of overlapping were assessed. 16 lesions were established as tumour persistence/recurrence by histological and clinical criteria. Three LGG and 1 HGG were positive on MR and negative on PET, all non-enhancing on post contrast MR. GS demonstrated disease. With a cut-off value of SUVmax 2.20, TBR 1.30 and TSR 0.90, a sensitivity of 87% was achieved in tumour assessment/ progression on DOPA PET. In most of the patients there was excellent overlapping between PET and MRI volumes (average 59%). In 3 patients there were mismatch of volumes (0 to 23%) with different areas of uptake/enhancement in the 2 modalities. Our preliminary results showed that DOPA PET is accurate for primary assessment/recurrence. In few cases there was a volume mismatch on uptake/enhancement/signal change, which might reflect different biological behaviors of the tumours.
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