Imaging of amide proton transfer and nuclear Overhauser enhancement in ischemic stroke with corrections for competing effects.
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ABSTRACT:
SUBMITTER: Li H
PROVIDER: S-EPMC4303585 | biostudies-other | 2015 Feb
REPOSITORIES: biostudies-other
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Project description:BackgroundAmide proton transfer (APT) imaging may help identify the ischaemic penumbra in stroke patients, the classical definition of which is a region of tissue around the ischaemic core that is hypoperfused and metabolically stressed. Given the potential of APT imaging to complement existing imaging techniques to provide clinically-relevant information, there is a need to develop analysis techniques that deliver a robust and repeatable APT metric. The challenge to accurate quantification of an APT metric has been the heterogeneous in-vivo environment of human tissue, which exhibits several confounding magnetisation transfer effects including spectrally-asymmetric nuclear Overhauser effects (NOEs). The recent literature has introduced various model-free and model-based approaches to analysis that seek to overcome these limitations.ObjectivesThe objective of this work was to compare quantification techniques for CEST imaging that specifically separate APT and NOE effects for application in the clinical setting. Towards this end a methodological comparison of different CEST quantification techniques was undertaken in healthy subjects, and around clinical endpoints in a cohort of acute stroke patients.MethodsMRI data from 12 patients presenting with ischaemic stroke were retrospectively analysed. Six APT quantification techniques, comprising model-based and model-free techniques, were compared for repeatability and ability for APT to distinguish pathological tissue in acute stroke.ResultsRobustness analysis of six quantification techniques indicated that the multi-pool model-based technique had the smallest contrast between grey and white matter (2%), whereas model-free techniques exhibited the highest contrast (>30%). Model-based techniques also exhibited the lowest spatial variability, of which 4-pool APTR∗ was by far the most uniform (10% coefficient of variation, CoV), followed by 3-pool analysis (20%). Four-pool analysis yielded the highest ischaemic core contrast-to-noise ratio (0.74). Four-pool modelling of APT effects was more repeatable (3.2% CoV) than 3-pool modelling (4.6% CoV), but this appears to come at the cost of reduced contrast between infarct growth tissue and normal tissue.ConclusionThe multi-pool measures performed best across the analyses of repeatability, spatial variability, contrast-to-noise ratio, and grey matter-white matter contrast, and might therefore be more suitable for use in clinical imaging of acute stroke. Addition of a fourth pool that separates NOEs and semisolid effects appeared to be more biophysically accurate and provided better separation of the APT signal compared to the 3-pool equivalent, but this improvement appeared be accompanied by reduced contrast between infarct growth tissue and normal tissue.
| S-EPMC6503165 | biostudies-literature
Project description:PurposeThe purpose is to evaluate the relative contribution from confounding factors (T1 weighting and magnetization transfer) to the CEST ratio (CESTR)-quantified amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) (-3.5) in tumors as well as whether the CESTR can reflect the distribution of the solute concentration (fs ).MethodsWe first provided a signal model that shows the separate dependence of CESTR on these confounding factors and the clean CEST/NOE effects quantified by an apparent exchange-dependent relaxation (AREX) method. We then measured the change in these effects in the 9-L tumor model in rats, through which we calculated the relative contribution of each confounding factor. fs was also fitted, and its correlations with the CESTR and AREX were assessed to evaluate their capabilities to reflect fs .ResultsThe CESTR-quantified APT shows "positive" contrast in tumors, which arises primarily from R1w at low powers and both R1w and magnetization transfer at high powers. CESTR-quantified NOE (-3.5) shows no or weak contrast in tumors, which is due to the cancelation of R1w and NOE (-3.5), which have opposite contributions. CESTR-quantified APT has a stronger correlation with APT fs than AREX-quantified APT. CESTR-quantified NOE (-3.5) has a weaker correlation with NOE (-3.5) fs than AREX-quantified NOE (-3.5).ConclusionCESTR reflects a combined effect of T1 weighting and CEST/NOE. Both factors depend on fs , which contributes positively to the dependence of CESTR on fs in APT imaging and enhances its correlation with fs . In contrast, these factors have opposite contributions to its dependence on fs in NOE (-3.5) imaging, thereby weakening the correlation.
| S-EPMC10616782 | biostudies-literature
Project description:PurposeChemical exchange saturation transfer (CEST) imaging measurement depends not only on the labile proton concentration and pH-dependent exchange rate but also on experimental conditions, including the relaxation delay and radiofrequency (RF) saturation time. Our study aimed to extend a quasi-steady-state (QUASS) solution to a modified multi-slice CEST MRI sequence and test if it provides enhanced pH imaging after acute stroke.MethodsOur study derived the QUASS solution for a modified multislice CEST MRI sequence with an unevenly segmented RF saturation between image readout and signal averaging. Numerical simulation was performed to test if the generalized QUASS solution corrects the impact of insufficiently long relaxation delay, primary and secondary saturation times, and multi-slice readout. In addition, multiparametric MRI scans were obtained after middle cerebral artery occlusion, including relaxation and CEST Z-spectrum, to evaluate the performance of QUASS CEST MRI in a rodent acute stroke model. We also performed Lorentzian fitting to isolate multi-pool CEST contributions.ResultsThe QUASS analysis enhanced pH-weighted magnetization transfer asymmetry contrast over the routine apparent CEST measurements in both contralateral normal (-3.46% ± 0.62% (apparent) vs. -3.67% ± 0.66% (QUASS), P < 0.05) and ischemic tissue (-5.53% ± 0.68% (apparent) vs. -5.94% ± 0.73% (QUASS), P < 0.05). Lorentzian fitting also showed significant differences between routine and QUASS analysis of ischemia-induced changes in magnetization transfer, amide, amine, guanidyl CEST, and nuclear Overhauser enhancement (-1.6 parts per million) effects.ConclusionOur study demonstrated that generalized QUASS analysis enhanced pH MRI contrast and improved quantification of the underlying CEST contrast mechanism, promising for further in vivo applications.
| S-EPMC9529238 | biostudies-literature
Project description:Background: Amide proton transfer (APT) MR imaging has shown great potential in the evaluation of stroke severity because of its sensitivity to acid environments. However, this promising MRI technique has not been used to assess treatment efficacy with regard to stroke recovery. Purpose: To assess the therapeutic effect of supportive treatment in ischemic stroke patients using the pH-sensitive APT MRI technique. Material and Methods: Forty-three ischemic stroke patients at an early stage were recruited and scanned with conventional and APT MRI sequences at 3T before treatment. After treatment, 26 patients underwent a follow-up MRI scan (one to three times on different days). The magnetization-transfer-ratio asymmetry at 3.5 ppm, usually called the APT-weighted (APTW) signal, was measured. The APTW signal changes following treatment were analyzed. Results: Baseline APTW signal intensities in the infarcted lesions inversely correlated with baseline stroke severity. Lesion APTW values gradually increased with time in 24 cases (92.3%) with a follow-up MRI scan, showing clinical symptom improvements. Two cases (7.7%) showed further decreased APTW signal in the follow-up scan, accompanied by clinical symptom aggravation. Compared to the baseline, significant APTW signal increases were found for all post-treatment patients (efficacious), whether based on post-treatment or on stroke onset times. The increase in APTW signal in the ischemic stroke lesion after treatment was associated with an improvement in clinical symptoms. Conclusion: The APTW signal would be a useful imaging biomarker by which to assess the therapeutic efficacy of ischemic stroke treatment.
| S-EPMC6395437 | biostudies-literature
Project description:ObjectivesTo quantify the brain maturation process during childhood using combined amide proton transfer (APT) and conventional magnetization transfer (MT) imaging at 3 Tesla.MethodsEighty-two neurodevelopmentally normal children (44 males and 38 females; age range, 2-190 months) were imaged using an APT/MT imaging protocol with multiple saturation frequency offsets. The APT-weighted (APTW) and MT ratio (MTR) signals were quantitatively analyzed in multiple brain areas. Age-related changes in MTR and APTW were evaluated with a non-linear regression analysis.ResultsThe APTW signals followed a decreasing exponential curve with age in all brain regions measured (R(2) = 0.7-0.8 for the corpus callosum, frontal and occipital white matter, and centrum semiovale). The most significant changes appeared within the first year. At maturation, larger decreases in APTW and lower APTW values were found in the white matter. On the contrary, the MTR signals followed an increasing exponential curve with age in the same brain regions measured, with the most significant changes appearing within the initial 2 years. There was an inverse correlation between the MTR and APTW signal intensities during brain maturation.ConclusionsTogether with MT imaging, protein-based APT imaging can provide additional information in assessing brain myelination in the paediatric population.Key points• APTW signals followed a decreasing exponential curve with age. • The most significant APTW changes appeared within the first year • At maturation, larger APTW decreases and lower APTW appeared in white matter • MTR signals followed an increasing exponential curve with age.
| S-EPMC5747245 | biostudies-literature
Project description:PurposeTo quantify amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) contributions to in vivo chemical exchange saturation transfer MRI signals in tumors.Theory and methodsTwo-pool (free water and semi-solid protons) and four-pool (free water, semi-solid, amide, and upfield NOE-related protons) tissue models combined with the super-Lorentzian lineshape for semi-solid protons were used to fit wide and narrow frequency-offset magnetization-transfer (MT) data, respectively. Extrapolated semi-solid MT signals at 3.5 and -3.5 ppm from water were used as reference signals to quantify APT and NOE, respectively. Six glioma-bearing rats were scanned at 4.7 Tesla. Quantitative APT and NOE signals were compared at three saturation power levels.ResultsThe observed APT signals were significantly higher in the tumor (center and rim) than in the contralateral normal brain tissue at all saturation powers, and were the major contributor to the APT-weighted image contrast (based on MT asymmetry analysis) between the tumor and the normal brain tissue. The NOE (a positive confounding factor) enhanced this APT-weighted image contrast. The fitted amide pool sizes were significantly larger, while the NOE-related pool sizes were significantly smaller in the tumor than in the normal brain tissue.ConclusionThe extrapolated semi-solid magnetization transfer reference provides a relatively accurate approach for quantitatively measuring pure APT and NOE signals.
| S-EPMC4561043 | biostudies-literature
Project description:PurposeIn chemical exchange saturation transfer imaging, saturation effects between - 2 to - 5 ppm (nuclear Overhauser effects, NOEs) have been shown to exhibit contrast in preclinical stroke models. Our previous work on NOEs in human stroke used an analysis model that combined NOEs and semisolid MT; however their combination might feasibly have reduced sensitivity to changes in NOEs. The aim of this study was to explore the information a 4-pool Bloch-McConnell model provides about the NOE contribution in ischemic stroke, contrasting that with an intentionally approximate 3-pool model.MethodsMRI data from 12 patients presenting with ischemic stroke were retrospectively analyzed, as well as from six animals induced with an ischemic lesion. Two Bloch-McConnell models (4 pools, and a 3-pool approximation) were compared for their ability to distinguish pathological tissue in acute stroke. The association of NOEs with pH was also explored, using pH phantoms that mimic the intracellular environment of naïve mouse brain.ResultsThe 4-pool measure of NOEs exhibited a different association with tissue outcome compared to 3-pool approximation in the ischemic core and in tissue that underwent delayed infarction. In the ischemic core, the 4-pool measure was elevated in patient white matter ( 1.20±0.20 ) and in animals ( 1.27±0.20 ). In the naïve brain pH phantoms, significant positive correlation between the NOE and pH was observed.ConclusionAssociations of NOEs with tissue pathology were found using the 4-pool metric that were not observed using the 3-pool approximation. The 4-pool model more adequately captured in vivo changes in NOEs and revealed trends depending on tissue pathology in stroke.
| S-EPMC9314583 | biostudies-literature
Project description:ImportanceThe process of brain development in children with developmental delay is not well known. Amide proton transfer-weighted (APTw) imaging is a novel molecular magnetic resonance imaging (MRI) technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides involved in the myelination process, and may be useful for providing insights into brain development.ObjectiveTo assess the contribution of amide proton transfer-weighted (APTw) imaging and magnetization transfer (MT) imaging to the evaluation of children with developmental delay (DD).MethodsFifty-one patients with DD were recruited to this study. The patients were divided into two groups according to the state of myelination assessed on conventional magnetic resonance imaging (MRI). Thirty patients (10 girls, 20 boys; age range: 1-8 months; median age: 4 months) in group A showed delayed myelination on MRI, while 21 patients (3 girls, 18 boys; age range: 12-36months; median age: 25months) in group B showed normal myelination on MRI. Fifty-one age- and sex-matched children with normal developmental quotient (DQ) and normal MRI appearance were recruited as normal controls. Three-slice APTw/MT axial imaging was performed at the level of the centrum semiovale, the basal ganglia and the pons. Quantitative data of the MT ratio (MTR) and APTw were analyzed for multiple brain regions. Independent-sample t-tests were used to compare differences in APTw and MTR signals between the two DD groups and normal controls. Analysis of Covariance was conducted to correct the statistical results. The level of statistical significance was set to P < 0.05.ResultsFor group A, the MTR values were lower in all regions (P = 0.004-0.033) compared with the normal controls, while the APTw values were higher in the pons, middle cerebellar peduncle, corpus callosum, frontal white matter, occipital white matter and centrum semiovale (P = 0.004-0.040 ). For Group B, the MTR values were slightly reduced, and the APTw values were slightly increased compared with the normal controls, but the differences were not statistically significant (P > 0.05).InterpretationFor DD patients showing signs of delayed myelination on MRI, MTR and APTw imaging can help to diagnose myelination delay by quantifying semi-solid macromolecules and cytosolic endogenous mobile proteins and peptides at a molecular level, providing a new method for comprehensive evaluation of DD. For DD patients with normal myelination on MRI, the clinical values of MTR and APTw imaging remain to be explored.
| S-EPMC7768295 | biostudies-literature
Project description:Amide proton transfer (APT) imaging is a variant of magnetization transfer (MT) imaging, in which the contrast is determined by a change in water intensity due to chemical exchange with saturated amide protons of endogenous mobile proteins and peptides. In this study, eight Fisher 344 rats implanted with 9L gliosarcoma cells and six nude rats implanted with human glioblastoma cells were imaged at 4.7 T. There were increased signal intensities in tumors in the APT-weighted images. The contrast of APT imaging between the tumor and contralateral brain tissue was about 3.9% in water intensity (1.49 +/- 0.66% vs -2.36 +/- 0.19%) for the more uniformly hypercellular 9L brain tumors, and it was reduced to 1.6% (-1.18 +/- 0.60% vs -2.77 +/- 0.42%) for the human glioblastoma xenografts that contained hypocellular zones of necrosis. The preliminary results show that the APT technique at the protein level may provide a unique MRI contrast for the characterization of brain tumors.
| S-EPMC2943209 | biostudies-other
Project description:Amide proton transfer-weighted (APTw) MRI is a novel molecular imaging technique that can noninvasively detect endogenous cellular proteins and peptides in tissue. Here, we demonstrate the feasibility of protein-based APTw MRI in characterizing amnestic mild cognitive impairment (aMCI). Eighteen patients with confirmed aMCI and 18 matched normal controls were scanned at 3 Tesla. The APTw, as well as conventional magnetization transfer ratio (MTR), signal differences between aMCI and normal groups were assessed by the independent samples t-test, and the receiver-operator-characteristic analysis was used to assess the diagnostic performance of APTw. When comparing the normal control group, aMCI brains typically had relatively higher APTw signals. Quantitatively, APTw intensity values were significantly higher in nine of 12 regions of interest in aMCI patients than in normal controls. The largest areas under the receiver-operator-characteristic curves were 0.88 (gray matter in occipital lobe) and 0.82 (gray matter in temporal lobe, white matter in occipital lobe) in diagnosing aMCI patients. On the contrary, MTR intensity values were significantly higher in only three of 12 regions of interest in the aMCI group. Additionally, the age dependency analyses revealed that these cross-sectional APTw/MTR signals had an increasing trend with age in most brain regions for normal controls, but a decreasing trend with age in most brain regions for aMCI patients. Our early results show the potential of the APTw signal as a new imaging biomarker for the noninvasive molecular diagnosis of aMCI.
| S-EPMC6948365 | biostudies-literature