Sensitivity of ACL volume and T21 relaxation time to magnetic resonance imaging scan conditions

Anterior cruciate ligament (ACL) volume and T₂¹ relaxation times from magnetic resonance (MR) images have been previously shown to predict the structural properties of healing ligaments. We investigated whether MR imaging scan resolution and condition (in vivo, in situ, or ex vivo) affected ACL volume and T₂¹ relaxation times in intact ligaments. ACLs of 14 pigs were imaged using a 3 T scanner and a six-channel flexcoil using at least two of four possible scan conditions: (1) in vivo moderate resolution (n = 14); (2) in vivo high resolution (n = 7); (3) in situ high resolution acquired within 60 minutes of euthanasia (n = 6); and (4) ex vivo high resolution following hind limb disarticulation and one freeze-thaw cycle (n = 7). T₂¹ relaxation times were mapped to the ACL voxels. The total ACL volume was then divided into four sub-volumes (Vol_1–4) based on predetermined increasing ranges of T₂¹ times. ACL T₂¹ statistics (first quartile, median, and standard deviation (SD)) were computed. Scan resolution had no effect on the total ACL volume, but Vol₁ and first quartile T₂¹ times decreased with high resolution and in situ/ex vivo scan conditions. The most dramatic differences in T₂¹ summary statistics were between in vivo moderate and ex vivo high resolution scan conditions that included a freeze-thaw cycle: ACL T₂¹ SD increased by over 50% in 9 animals, and more than 90% in 4 animals. Our results indicated that T₂¹-based prediction models to quantify in vivo structural properties of healing ligaments should be based on high resolution in vivo MR scan conditions.     

Synergistic enhancement of iron oxide nanoparticle and gadolinium for dual-contrast MRI

PurposeThe use of MR contrast agents allows accurate diagnosis by exerting an influence on the longitudinal (T₁) or transverse (T₂) relaxation time of the surrounding tissue. In this study, we combined the use of iron oxide (IO) particles and nonspecific extracellular gadolinium chelate (Gd) in order to further improve the sensitivity and specificity of lesion detection.ProceduresWith a 7-Tesla scanner, pre-contrasted, IO-enhanced and dual contrast agent enhanced MRIs were performed in phantom, normal animals, and animal models of lymph node tumor metastases and orthotopic brain tumor. For the dual-contrast (DC) MRI, we focused on the evaluation of T₂ weighted DC MRI with IO administered first, then followed by the injection of a bolus of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA).ResultsBased on the C/N ratios and MRI relaxometry, the synergistic effect of coordinated administration of Gd-DTPA and IO was observed and confirmed in phantom, normal liver and tumor models. At 30 min after administration of Feridex, Gd-DTPA further decreased T₂ relaxation in liver immediately after the injection. Additional administration of Gd-DTPA also immediately increased the signal contrast between tumor and brain parenchyma and maximized the C/N ratio to ?4.12 ± 0.71. Dual contrast MRI also enhanced the delineation of tumor borders and small lesions.ConclusionsDC-MRI will be helpful to improve diagnostic accuracy and decrease the threshold size for lesion detection.     

Neonatal brain: Fabrication of a tissue-mimicking phantom and optimization of clinical Τ1w and T2w MRI sequences at 1.5 T

PurposeTο fabricate a tissue-mimicking phantom simulating the MR relaxation times of neonatal gray and white matter at 1.5 T, for the optimization of clinical Τ1 weighted (T1w) and T2 weighted (T2w) sequences.MethodsNumerous agarose gel solutions, doped with paramagnetic Gadopentetic acid (Gd-DTPA) ions, underwent quantitative relaxometry with a Turbo-Inversion-Recovery Spin-Echo (TIRSE) sequence and a Car-Purcell-Meiboom-Gill (CPMG) sequence for T1 and T2 measurements, respectively. Twenty samples which simulated the spectrum of relaxation times of neonatal brain parenchyma were selected. Reproducibility was tested by refabrication and relaxometry of the relevant samples while stability was tested by six sets of quantitative relaxometry scans during a 12-month period.Results“Neonatal gray matter equivalent”(0.6%w/v agarose-0.10 mM Gd-DTPA), accurately mimicked relaxation times of neonatal gray matter: T1 = (1134 ± 7)ms, T2 = (200 ± 7)ms. “Neonatal white matter equivalent”(0.3%w/v agarose-0.03 mM Gd-DTPA), accurately mimicked relaxation times of neonatal white matter: T1 = (1654 ± 9)ms, T2 = (376 ± 4)ms. Coefficient of variation of T1 and T2 relaxation times measurements remained less than 5% during 12 months. Sequences were modified according to maximum relative contrast (RC) between neonatal gray and white matter equivalents. Optimized T2wTSE and T1wTSE parameters were TR/TE = 9500 ms/280 ms and TR/TE = 1200 ms/10 ms, respectively for a MAGNETOM Vision/Sonata Hybrid 1.5 T system. Quantitative relaxometry at different 1.5 T MR systems resulted in inter-system T1, T2 measurement deviations of 12% and 3%, respectively.ConclusionA precise, stable and reproducible phantom for the neonatal brain was fabricated. Subsequent optimization of clinical T1w and T2w sequences based on maximum RC between neonatal gray and white matter equivalents was scientifically supported with robust relaxometry. The procedure was applicable in different 1.5 T systems.HighlightTR & TE optimization of neonatal brain at 1.5 T was based on relaxometry of a stable, reproducible phantom.     

Multiparametric MRI-based radiomics analysis for the prediction of breast tumor regression patterns after neoadjuvant chemotherapy

ObjectivesBreast cancers show different regression patterns after neoadjuvant chemotherapy. Certain regression patterns are associated with more reliable margins in breast-conserving surgery. Our study aims to establish a nomogram based on radiomic features and clinicopathological factors to predict regression patterns in breast cancer patients.MethodsWe retrospectively reviewed 144 breast cancer patients who received neoadjuvant chemotherapy and underwent definitive surgery in our center from January 2016 to December 2019. Tumor regression patterns were categorized as type 1 (concentric regression + pCR) and type 2 (multifocal residues + SD + PD) based on pathological results. We extracted 1158 multidimensional features from 2 sequences of MRI images. After feature selection, machine learning was applied to construct a radiomic signature. Clinical characteristics were selected by backward stepwise selection. The combined prediction model was built based on both the radiomic signature and clinical factors. The predictive performance of the combined prediction model was evaluated.ResultsTwo radiomic features were selected for constructing the radiomic signature. Combined with two significant clinical characteristics, the combined prediction model showed excellent prediction performance, with an area under the receiver operating characteristic curve of 0.902 (95% confidence interval 0.8343–0.9701) in the primary cohort and 0.826 (95% confidence interval 0.6774–0.9753) in the validation cohort.ConclusionsOur study established a unique model combining a radiomic signature and clinicopathological factors to predict tumor regression patterns prior to the initiation of NAC. The early prediction of type 2 regression offers the opportunity to modify preoperative treatments or aids in determining surgical options.     

Breast fine-needle aspiration malondialdehyde deoxyguanosine adduct in breast cancer

Abstract

This study has analysed the generation of 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adduct [M₁dG], a biomarker of oxidative stress and lipid peroxidation, in breast fine-needle aspirate samples of 22 patients with breast cancer, at different clinical stages, in respect to 13 controls. The multivariate analysis show that M₁dG adduct was higher in cases than in controls (Mean Ratio (MR) = 5.26, 95% CI = 3.16–8.77). Increased M₁dG was observed in women with a tumour grade 3 and a pathological diameter 2 (MR = 7.61, 95% CI = 3.91–14.80 and MR = 5.75, 95% CI = 3.13–10.59, respectively). A trend with increasing tumour grade and pathological diameter was present (MR = 1.98, 95% CI = 1.57–2.50 and MR = 2.44, 95% CI = 1.71–3.48, respectively). Not significant effects of age and smoking habit were found (MR = 1.58, 95% CI = 0.92–2.72 and MR = 1.68, 95% CI 0.88–3.20, respectively). An increment over the background frequency of M₁dG can contribute to breast cancer development. Increasing severity of breast tumour can influence DNA damage level.     

In Vivo MRI Assessment of Hepatic and Splenic Disease in a Murine Model of Schistosmiasis

BackgroundSchistosomiasis (or bilharzia), a major parasitic disease, affects more than 260 million people worldwide. In chronic cases of intestinal schistosomiasis caused by trematodes of the Schistosoma genus, hepatic fibrosis develops as a host immune response to the helminth eggs, followed by potentially lethal portal hypertension. In this study, we characterized hepatic and splenic features of a murine model of intestinal schistosomiasis using in vivo magnetic resonance imaging (MRI) and evaluated the transverse relaxation time T₂ as a non-invasive imaging biomarker for monitoring hepatic fibrogenesis.Conclusions/SignificanceOur multiparametric MRI approach confirms that this murine model replicates hepatic and splenic manifestations of human intestinal schistosomiasis. Quantitative T₂ mapping proved sensitive to assess liver fibrogenesis non-invasively and may therefore constitute an objective imaging biomarker for treatment monitoring in diseases involving hepatic fibrosis.     

Simulation of images of CDMAM phantom and the estimation of measurement uncertainties of threshold gold thickness

PurposeTo demonstrate a method of simulating mammography images of the CDMAM phantom and to investigate the coefficient of variation (CoV) in the threshold gold thickness (t_T) measurements associated with use of the phantom.MethodsThe noise and sharpness of Hologic Dimensions and GE Essential mammography systems were characterized to provide data for the simulation. The simulation method was validated by comparing the t_T results of real and simulated images of the CDMAM phantom for three different doses and the two systems. The detection matrices produced from each of 64 images using CDCOM software were randomly resampled to create 512 sets of 8, 16 and 32 images to estimate the CoV of t_T. Sets of simulated images for a range of doses were used to estimate the CoVs for a range of diameters and threshold thicknesses.ResultsNo significant differences were found for t_T or the CoV between real and simulated CDMAM images. It was shown that resampling from 256 images was required for estimating the CoV. The CoV was around 4% using 16 images for most of the phantom but is over double that for details near the edge of the phantom.ConclusionsWe have demonstrated a method to simulate images of the CDMAM phantom for different systems at a range of doses. We provide data for calculating uncertainties in t_T. Any future review of the European guidelines should take into consideration the calculated uncertainties for the 0.1 mm detail.     

High Temporal Resolution Parametric MRI Monitoring of the Initial Ischemia/Reperfusion Phase in Experimental Acute Kidney Injury

Ischemia/reperfusion (I/R) injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI). There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive in vivo parametric magnetic resonance imaging (MRI) may elucidate spatio-temporal pathophysiological changes in the kidney by monitoring the MR relaxation parameters T₂* and T₂, which are known to be sensitive to blood oxygenation. The aim of our study was to establish the technical feasibility of fast continuous T₂*/T₂ mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Significant changes in T₂* and T₂ were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for in-vivo monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI.     

Texture analysis of cartilage T<Subscript>2</Subscript> maps: individuals with risk factors for OA have higher and more heterogeneous knee cartilage MR T<Subscript>2</Subscript> compared to normal controls - data from the osteoarthritis initiative

Introduction  

The goals of this study were (i) to compare the prevalence of focal knee abnormalities, the mean cartilage T₂ relaxation time, and the spatial distribution of cartilage magnetic resonance (MR) T₂ relaxation times between subjects with and without risk factors for Osteoarthritis (OA), (ii) to determine the relationship between MR cartilage T₂ parameters, age and cartilage morphology as determined with whole-organ magnetic resonance imaging scores (WORMS) and (iii) to assess the reproducibility of WORMS scoring and T₂ relaxation time measurements including the mean and grey level co-occurrence matrix (GLCM) texture parameters.     

31P nuclear magnetic resonance studies of the association of basic proteins with multilayers of diacyl phosphatidylserine

Lysozyme, cytochrome c, poly(l-lysine), myelin basic protein and ribonuclease were used to form multilayer dispersions containing about 50% protein (by weight) with bovine brain diacyl phosphatidylserine (PS). ³¹P nuclear magnetic resonance shift anisotropies, spin-spin (T₂) and spin-lattice (T₁) relaxation times for the lipid headgroup phosphorus were measured at 36.44 MHz. At pH 7.5, lysozyme, cytochrome c, poly(l-lysine) and ribonuclease were shown to increase the chemical shift anisotropy of PS by between 12–20%. Myelin basic protein altered the shape of the phosphate resonance, suggesting the presence of two lipid components, one of which had a modified headgroup conformation. The presence of cytochrome c led to the formation of a narrow spike at the isotropic shift position of the spectrum. Of the various proteins or peptides we have studied, only poly(l-lysine) and cytochrome c had any effect on the T₁ of PS (1050 ms). Both caused a 20–30% decrease in T₁ of the lamellar-phase phosphate peak. The narrow peak in the presence of cytochrome c had a very short T₁ of 156 ms. The possibility is considered that the cytochrome Fe³⁺ contributes to the phosphate relaxation in this case. The effect of all proteins on the T₂ of the phosphorus resonance was to cause an increase from the value for pure PS (1.6 ms) to between 2 and 5 ms. The results obtained with proteins are compared with the effects of small ions and intrinsic membrane proteins on the order and motion of the headgroups of lipids in bilayers.     

High Dynamic Range Processing for Magnetic Resonance Imaging

Purpose

To minimize feature loss in T₁- and T₂-weighted MRI by merging multiple MR images acquired at different T_R and T_E to generate an image with increased dynamic range.

Materials and Methods

High Dynamic Range (HDR) processing techniques from the field of photography were applied to a series of acquired MR images. Specifically, a method to parameterize the algorithm for MRI data was developed and tested. T₁- and T₂-weighted images of a number of contrast agent phantoms and a live mouse were acquired with varying T_R and T_E parameters. The images were computationally merged to produce HDR-MR images. All acquisitions were performed on a 7.05 T Bruker PharmaScan with a multi-echo spin echo pulse sequence.

Results

HDR-MRI delineated bright and dark features that were either saturated or indistinguishable from background in standard T₁- and T₂-weighted MRI. The increased dynamic range preserved intensity gradation over a larger range of T₁ and T₂ in phantoms and revealed more anatomical features in vivo.

Conclusions

We have developed and tested a method to apply HDR processing to MR images. The increased dynamic range of HDR-MR images as compared to standard T₁- and T₂-weighted images minimizes feature loss caused by magnetization recovery or low SNR.     

Intérêt de l’imagerie hybride TEMP/TDM pour la scintigraphie des récepteurs de la somatostatine dans le bilan des tumeurs endocrines gastro-entéro-pancréatiques

In this work, we have evaluated the potential of image fusion and attenuation correction (AC) of SPECT-CT imaging for the assessment of gastro-entero-pancreatic endocrine tumors by somatostatin receptor scintigraphy (SRS).MethodAfter optimisation of acquisition and reconstruction parameters, we have evaluated, in a prospective study, SRS performed over a period of one year. We have compared visual interpretations of planar and tomographic images versus SPECT/CT images to determine if anatomical localisation and diagnostic contributions are improved. In a semi-quantitative analysis of pathological foci, we have measured maximal intensity values (T_max), tumour to background ratios (T/B) and tumour contrasts (Ct) with and without AC.ResultsIn 25 SRS, visual analysis has shown anatomical localisation improvements in 60% of cases (CI95%, 39–79) and diagnostic improvements in 64% of cases (CI95%, 43–82). Doubtful foci proportion changed from 44 to 11%. In the semi-quantitative analysis of 41 pathological foci, Wilcoxon matched-pairs tests showed significantly higher T_max, T/B and Ct values after AC.ConclusionSPECT/CT imaging improves diagnostic quality of SRS thanks to a better foci localisation and a better lesional contrast in the image.     

Relationship between T1rho magnetic resonance imaging,synovial fluid biomarkers,and the biochemical and biomechanical properties of cartilage

Non-invasive techniques for quantifying early biochemical and biomechanical changes in articular cartilage may provide a means of more precisely assessing osteoarthritis (OA) progression. The goals of this study were to determine the relationship between T1rho magnetic resonance (MR) imaging relaxation times and changes in cartilage composition, cartilage mechanical properties, and synovial fluid biomarker levels and to demonstrate the application of T1rho imaging to evaluate cartilage composition in human subjects in vivo. Femoral condyles and synovial fluid were harvested from healthy and OA porcine knee joints. Sagittal T1rho relaxation MR images of the condyles were acquired. OA regions of OA joints exhibited an increase in T1rho relaxation times as compared to non-OA regions. Furthermore in these regions, cartilage sGAG content and aggregate modulus decreased, while percent degraded collagen and water content increased. In OA joints, synovial fluid concentrations of sGAG decreased and C2C concentrations increased compared to healthy joints. T1rho relaxation times were negatively correlated with cartilage and synovial fluid sGAG concentrations and aggregate modulus and positively correlated with water content and permeability. Additionally, we demonstrated the application of these in vitro findings to the study of human subjects. Specifically, we demonstrated that walking results in decreased T1rho relaxation times, consistent with water exudation and an increase in proteoglycan concentration with in vivo loading. Together, these findings demonstrate that cartilage MR imaging and synovial fluid biomarkers provide powerful non-invasive tools for characterizing changes in the biochemical and biomechanical environments of the joint.     

1H NMRD studies of solutions of paramagnetic metal ions in ethyleneglycol

Solvent¹H T^?1₁ values at magnetic fields between 2.3 × 10^?4 and 1.2 T were measured for ethyleneglycol solutions of manganese(II), cobalt(II), nickel(II), copper(II), and gadolinium(III) salts in the temperature range ?10–+40 °C. The T^?1₁ profiles were interpreted on the ground of the available theories according to whether the electronic relaxation times or the rotational times are the correlation times for the interaction. The comparison among systems experiencing different correlation times and electronic structures (metal ions in water, ethyleneglycol, and in proteins) allowed us to test the general theoretical approach regarding nuclear relaxation times in paramagnetic systems. Such theoretical approaches allow researchers to extract structural parameters and information on the correlation times and dynamic processes operative in the various investigated systems.     

High-resolution 3D ultra-short echo time MRI with Rosette k-space pattern for brain iron content mapping

BackgroundThe iron concentration increases during normal brain development and is identified as a risk factor for many neurodegenerative diseases, it is vital to monitor iron content in the brain non-invasively.PurposeThis study aimed to quantify in vivo brain iron concentration with a 3D rosette-based ultra-short echo time (UTE) magnetic resonance imaging (MRI) sequence.MethodsA cylindrical phantom containing nine vials of different iron concentrations (iron (II) chloride) from 0.5 millimoles to 50 millimoles and six healthy subjects were scanned using 3D high-resolution (0.94 ×0.94 ×0.94 mm³) rosette UTE sequence at an echo time (TE) of 20 μs.ResultsIron-related hyperintense signals (i.e., positive contrast) were detected based on the phantom scan, and were used to establish an association between iron concentration and signal intensity. The signal intensities from in vivo scans were then converted to iron concentrations based on the association. The deep brain structures, such as the substantia nigra, putamen, and globus pallidus, were highlighted after the conversion, which indicated potential iron accumulations.ConclusionThis study suggested that T₁-weighted signal intensity could be used for brain iron mapping.     

Nuclear magnetic resonance relaxation times and plasmalemma water exchange in ivy bark

Measurement of nuclear magnetic resonance (NMR) relaxation times (transverse [T₂] and longitudinal [T₁]) for Hedera helix L. cv. Thorndale (ivy) bark water indicates the presence of at least two populations of water with different relaxation characteristics. One population of water with short T₂ and T₁ was found to be composed of both hydration water and extracellular free water. The second population of water with long T₂ and T₁ was identified as intracellular bulk water.     

Effects of temperature and field strength on the NMR relaxation times of 23Na in frog striated muscle

Pulsed NMR techniques have been applied to the study of the relaxation parameters characterizing ²³Na within frog striated muscle. Experiments were performed at 3°C, 22–24°C and 39°C at a Larmor frequency of 15.7 MHz; at 22–24°C, measurements were obtained both at 15.7 MHz and at 7.85 MHz.As previously reported, only a single spine-lattice relaxation time (T₁) was observed, but both slow (T₂)_I and fast (T₂)_II components of the spin-spin relaxation time were measured. The effect of temperature (θ) upon (1/T₁) was qualitatively similar to that reported for ²³Na in free solution; (θ) did not significantly affect (1/T₂) over the range of temperatures studied. (1/T₂)_I, and to a lesser degreee, (1/T₁) exhibited a modest inverse dependence of doubtful significance on the Larmor frequency.The data are examined within the framework of a simple specific model; a conservative values in assumed for the quadrupolar coupling constant characterizing immobilized intracellular Na⁺. Within this framework, the results suggest that the fraction of bound ions whose molecular tumbling is severely restricted does not exceed some few percent of the total sodium population.     

Model-Based Acceleration of Look-Locker T1 Mapping

Mapping the longitudinal relaxation time T ₁ has widespread applications in clinical MRI as it promises a quantitative comparison of tissue properties across subjects and scanners. Due to the long scan times of conventional methods, however, the use of quantitative MRI in clinical routine is still very limited. In this work, an acceleration of Inversion-Recovery Look-Locker (IR-LL) T ₁ mapping is presented. A model-based algorithm is used to iteratively enforce an exponential relaxation model to a highly undersampled radially acquired IR-LL dataset obtained after the application of a single global inversion pulse. Using the proposed technique, a T ₁ map of a single slice with 1.6mm in-plane resolution and 4mm slice thickness can be reconstructed from data acquired in only 6s. A time-consuming segmented IR experiment was used as gold standard for T ₁ mapping in this work. In the subsequent validation study, the model-based reconstruction of a single-inversion IR-LL dataset exhibited a T ₁ difference of less than 2.6% compared to the segmented IR-LL reference in a phantom consisting of vials with T ₁ values between 200ms and 3000ms. In vivo, the T ₁ difference was smaller than 5.5% in WM and GM of seven healthy volunteers. Additionally, the T ₁ values are comparable to standard literature values. Despite the high acceleration, all model-based reconstructions were of a visual quality comparable to fully sampled references. Finally, the reproducibility of the T ₁ mapping method was demonstrated in repeated acquisitions. In conclusion, the presented approach represents a promising way for fast and accurate T ₁ mapping using radial IR-LL acquisitions without the need of any segmentation.     

Combined Metaheuristic Algorithm and Radiomics Strategy for the Analysis of Neuroanatomical Structures in Schizophrenia and Schizoaffective Disorders

ObjectivesSchizophrenia (SZ) is the most chronic disabling psychotic brain disorder. It is characterized by delusions and auditory hallucinations, as well as impairments in memory. Schizoaffective (SA) signs are co-morbid with SZ and are characterized by symptoms of SZ and mood disorder. Various researches suggest that SZ and SA share a number of equally severe cognitive deficits, but the pathophysiology has not yet been addressed in a comprehensive way. In this work, the heterogeneity in whole brain, ventricle and cerebellum region from psychotic MR brain images is examined using Machine learning and radiomic features.Materials and methodsT1 weighted MR brain images are obtained from Schizconnect database for the analysis. The shape prior level set method is used to segment the ventricle and cerebellum structures. The radiomic features which include shape and texture are extracted from these regions to discriminate the SZ and SA subjects. The performance of these features is evaluated with Binary Particle Swarm Optimization (BPSO) based Fuzzy Support Vector Machine (FSVM) classifier.ResultsThe shape constrained Level Set method is able to better segment ventricles and cerebellum regions from the images. The significant features that are extracted from whole brain, ventricle and cerebellum are identified by the BPSO based FSVM. The combination of radiomic features extracted from cerebellum region achieved high classification accuracy (90.09%) using metaheuristic algorithm. The extracted features from cerebellum are correlated with PANSS score. The causal analysis shows that there is an association been the tissue texture variation in identifying the disease severity. The symmetry analysis shows that left brain mean area is larger than the right side area. In particular SA has low cerebellum area compared to SZ. The radiomic features such as Hermite, Laws and tensor extracted from the left cerebellum show a significant texture variation in all the considered subjects (p<0.0001).ConclusionsThe results are clinically relevant in discriminating the pattern change in the structure, hence this biomarker and frame work could be used for the severity study of psychotic disorders.