scholarly journals Mapping prion pathology in mice using quantitative imaging: an MRI study

2021 ◽  
Author(s):  
Eleni Demetriou ◽  
Mohamed Tachrount ◽  
Matthew Ellis ◽  
Jackeline Linehan ◽  
Sebastian Brandner ◽  
...  

Human prion diseases are fatal neurodegenerative disorders which cause cognitive impairment and neurological deficits. Additional measures of tissue status are necessary for improving the sensitivity and specificity of clinical diagnosis as in many cases clinical forms of prion disease are commonly mistaken for other forms of dementia. To that effect, we developed a set of quantitative magnetic resonance-based tools, including magnetic resonance spectroscopy (MRS), magnetization transfer ratio (MTR) and quantitative T1 and T2 imaging to study the course of the disease in an animal model of prion disease. Using in vivo MTR, significant changes were detected in the cortex and thalamus of late-stage prion -infected mice as compared to littermates. In addition, we found a significant increase of MTR in thalamus and cortex of 80 dpi healthy mice when compared with 160 dpi healthy mice suggestive of changes occurring during the development of the brain. Using quantitative T2 mapping, significantly higher values were measured in thalamus of prion mice at all stages of the disease (T2=40ms) while T1 was found to be significantly higher in cortex (T1=1.89s) and hippocampus, albeit only in late-stage prion mice as compared to aged-matched controls (T1=1.67s). Using quantitative MRS significant changes were detected in glutamate (Glu) and myo-inositol (Ins) at all stages of prion disease when compared with the control group. NAA, Cr, Lactate and Lipids were only found to be significantly different at early and late stages of the disease while Taurine (Tau) was only significantly increased in the asymptomatic stage without any significant change at early and late stages of the disease. These changes in MRI and MRS signals, which precede clinical signs of disease, could provide insights into the pathogenesis of this disease and may enable early detection of pathology.

2021 ◽  
Author(s):  
Xiaohan Yuan ◽  
Xiaomei Zhu ◽  
Yang Chen ◽  
Wangyan Liu ◽  
Wen Qian ◽  
...  

Abstract Background: Energetics alteration plays a key role in the process of myocardial injury in chronic hypoxic diseases (CHD). 31P magnetic resonance spectroscopy (MRS) can investigate alterations in cardiac energetics in vivo. This study was aimed to characterize the potential value of 31P MRS in evaluating cardiac energetics alteration of chronic hypoxia rats (CHR).Methods: Twenty-four CHRs were induced by SU5416 combined with hypoxia, and six rats were raised as control group. 31P MRS was performed weekly and the ratio of concentrations of phosphocreatine (PCr) to adenosine triphosphate (ATP) (PCr/ATP) was obtained. The index of cardiac structure and systolic function parameters, including the right ventricular function (RVEF), right ventricular end-diastolic volume index (RVEDVi), right ventricular end-systolic volume index (RVESVi), the left ventricular function parameters were also measured.Results: The declension of resting cardiac PCr/ATP ratio in CHR was observed at the 1st week, compared to control group (2.90±0.35 vs. 3.31±0.45, p =0.045), while the RVEF,RVEDVi and RVESVi decreased at the 2nd week (p<0.05). The PCr/ATP ratio displayed a significant correlation with RVEF(r = 0.605, p = 0.001),RVEDVi and RVESVi (r = -0.661, r = -0.703; p<0.001).Conclusions: 31P MRS can early detect the cardiac energetics alteration in CHR model before the onset of ventricular dysfunction. The decrease of PCr/ATP ratio likely revealed myocardial injury and cardiac dysfunction.


2003 ◽  
Vol 9 (6) ◽  
pp. 554-565 ◽  
Author(s):  
J P Ranjeva ◽  
J Pelletier ◽  
S Confort-Gouny ◽  
D Ibarrola ◽  
B Audoin ◽  
...  

A trophy of corpus callosum (C C) related to axonal loss has previously been observed in patients at the early stage of clinically definite multiple sclerosis (CDMS). Atrophy increases with the progression of the disease. Nevertheless, no data concerning the onset of atrophy of C C are currently available. The purpose of this study is to determine if damage in callosal tissue was present at the earliest stage of MS, in a subgroup of patients presenting with a clinically isolated syndrome suggestive of MS (C ISSMS), fulfilling the dissemination in space criteria according to McDonald. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) techniques were applied to measure C C volume, magnetization transfer ratio (MTR), mean diffusivity (MD), N-acetyl aspartate/choline-containing compounds (NAA/C ho) ratio, N-acetyl aspartate/total creatine (NA A/C r) ratio and C ho/C r ratio inside the C C of 46 C ISSMS patients and 24 sexand age-matched controls. No atrophy of C C was observed in the C ISSMS group. C C of patients was character ized by decreased MTR and increased MD. No change in the NA A/C r ratio was observed while the NA A/C ho ratio decreased and C ho/C r ratio increased in the splenium and the central anterio r part of C C. These abnormalities were present in patients with, but also without, macroscopic lesions inside the C C. O ur results indicate that diffuse structural and metabolic changes, which may be interpreted as representing predominantly myelin patho logy, occur in the C C at the earliest stage of MS before any atrophy is detected.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Radoslaw Magierski ◽  
Tomasz Sobow

Dementia with Lewy bodies (DLB) is considered to be the second most frequent primary degenerative dementing illness after Alzheimer’s disease (AD). DLB, together with Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD) belong toα-synucleinopathies—a group of neurodegenerative diseases associated with pathological accumulation of theα-synuclein protein. Dementia due to PD and DLB shares clinical symptoms and neuropsychological profiles. Moreover, the core features and additional clinical signs and symptoms for these two very similar diseases are largely the same. Neuroimaging seems to be a promising method in differential diagnosis of dementia studies. The development of imaging methods or other objective measures to supplement clinical criteria for DLB is needed and a method which would accurately facilitate diagnosis of DLB prior to death is still being searched. Proton magnetic resonance spectroscopy (1H-MRS) provides a noninvasive method of assessing anin vivobiochemistry of brain tissue. This review summarizes the main results obtained from the application of neuroimaging techniques in DLB cases focusing on1H-MRS.


Author(s):  
Lei Shi ◽  
Kexin Wang ◽  
Jinghong Yu ◽  
Mingkai Li ◽  
Guangmei Men ◽  
...  

Abstract Objective To investigate the relationship between quantitative analysis of MRI (T2-mapping) and the expression of matrix metalloproteinase (MMP-1, MMP-3) in osteoarthritis of the knee joint and the role of MMP-1,3 in the pathogenesis of osteoarthritis. Methods Thirty cases of knee osteoarthritis (KOA) patients with total knee arthroplasty (TKA) (lesion group) and 30 healthy adult volunteers (control group) were scanned with 1.5 T routine MR and T2-mapping, and their T2 values were measured and statistically analyzed. The pathological examination of the knee cartilage that was replaced during the operation and the immunohistochemical assay were used to measure the expression of MMP-1,3. The correlation between the T2 value of magnetic resonance imaging and the expression of MMP-1,3 was analyzed. Results (1) According to the Recht grading standard for magnetic resonance, the T2 value of magnetic resonance increased significantly with the increase of cartilage degeneration. The differences in T2 values between each level and the normal group were statistically significant (P  < 0.05). (2) The T2 value of magnetic resonance imaging increased with the severity of the cartilage degeneration pathological Mankin grading, and the difference was statistically significant (P  <  0.05). (3) The expression of MMP-1,3 increased with cartilage degeneration. (4) The T2 value and the expression of MMP-1 in cartilage showed a linear trend. The result of Spearman correlation analysis showed that the expression of MMP-1,3 increased as the cartilage T2 value increased. There was a positive linear correlation between the two. Conclusion The T2 value of magnetic resonance increased with the degeneration of KOA cartilage. The expression of MMP-1,3 increased with the severity of articular cartilage destruction. The T2 value of KOA magnetic resonance was positively correlated with the expression of MMP-1,3.


2018 ◽  
Vol 6 (12) ◽  
pp. 2348-2353
Author(s):  
Seyyed Arash Mahdawy ◽  
Babak Shekarchi ◽  
Mahshid Zaman

BACKGROUND:  During the eight years of the imposed war, Iraq used various chemical agents such as sulfur mustard and nerve agents (mainly tabun and sometimes soman) on Iran's soldiers. Using information obtained from specialist sequences and analysing information obtained from magnetic resonance imaging (MRI) in a susceptibility weighted imaging (SWI) sequence and magnetic resonance spectroscopy (MRS) provides valuable information on continuation of treatment and identifying functional disorders. AIM: The objective of this research was to evaluate the rate of metabolic variations in chemically injured veterans based on chemical neuromarkers using the chemical sequence MRS, which would help patients and physicians in terms of time, economics, and selection of appropriate therapeutic methods, so if the can physician can get complete information about the metabolic properties of the brain through paraclinical (especially MRI) tools before treatment, he might change his treatment program to reduce the complications caused by it. METHODOLOGY: In this research, 40 chemically injured veterans with brain dysfunction admitted to the screening centre for MRI with specialized MRS sequence participated. Accordingly, we examined the rate of brain metabolic variations about the level of neuromarkers and evaluated the relationship between the level of neuromarkers and brain damages. RESULTS: The results of this research revealed that while the demographic characteristics such as age of the two groups of chemically injured veterans and control was similar, only the median of the NAA/Cr (N-acetylaspartate to creatine ratio) ratio in PONS of chemically injured patients was significantly lower than that of the control group, and this ratio was similar in other parts of the brain in two groups. The results also showed that the ratio of NAA to total choline and Cr was similar in all parts of the brain in two groups. CONCLUSION: Based on the research results, using the MR (Magnetic Resonance) spectroscopy device and determination of the value and ratio of markers such as creatinine and N-acetylaspartate and choline, the brain injuries of chemically injured veterans can be examined. By conducting further studies and larger sample size, the brain damages in veterans can be diagnosed early, which would be a great contribution in their treatment.


2017 ◽  
Vol 32 (8) ◽  
pp. 731-739 ◽  
Author(s):  
Hiromichi Ito ◽  
Kenji Mori ◽  
Masafumi Harada ◽  
Sonoka Hisaoka ◽  
Yoshihiro Toda ◽  
...  

The pathophysiology of autism spectrum disorder (ASD) is not fully understood. We used proton magnetic resonance spectroscopy to investigate metabolite concentration ratios in the anterior cingulate cortex and left cerebellum in ASD. In the ACC and left cerebellum studies, the ASD group and intelligence quotient- and age-matched control group consisted of 112 and 114 subjects and 65 and 45 subjects, respectively. In the ASD group, γ-aminobutyric acid (GABA)+/ creatine/phosphocreatine (Cr) was significantly decreased in the anterior cingulate cortex, and glutamate (Glu)/Cr was significantly increased and GABA+/Cr was significantly decreased in the left cerebellum compared to those in the control group. In addition, both groups showed negative correlations between Glu/Cr and GABA+/Cr in the left cerebellum, and positive correlations between GABA+/Cr in the anterior cingulate cortex and left cerebellum. ASD subjects have hypoGABAergic alterations in the anterior cingulate cortex and hyperglutamatergic/hypoGABAergic alterations in the left cerebellum.


2019 ◽  
Author(s):  
Mohammad Vafaee-Shahi ◽  
Saeide Ghasemi ◽  
Mehran Beiraghi Toosi ◽  
Mahmoud Reza Ashrafi ◽  
Reza Shervin Badv ◽  
...  

Abstract Background: Leigh syndrome (LS) is a rare and inherited disease which is associated with progressive neurological disorders. The molecular underlying mechanism in LS is defined with some defects in mitochondrial respiratory chain enzymes. Case presentation: Here, an 8-year-old girl is reported with bilateral horizontal gaze palsy, ataxia and drowsiness. She developed unsteady gait, drowsiness, progressive ataxia and intention tremor during her admission period. The laboratory tests were reported within normal values including biochemical, hematological, immunological, infectious and inflammatory markers and blood and cerebrospinal fluid (CSF) lactate. Brain magnetic resonance imaging (MRI) demonstrated dorsal midbrain, bilateral putamen nuclei and cerebellar dentate nucleus involvement. Ocular examination revealed retinal atrophy and pale disk in both sides. These symptoms were in favor of a neurodegenerative disorder. Magnetic resonance spectroscopy (MRS) revealed an elevated lactate peak in involved areas which suggested a mitochondrial disease. Finally, the molecular genetic test reported NDUFS4 gene mutation which confirmed the presence of Leigh syndrome. She responded significantly to mitochondrial treatment cocktail and clinical signs and symptoms improved gradually. NDFUS4 gene encodes a subunit of mitochondrial complex I (NADH: ubiquinone oxidoreductase) that removes electrons from NADH and transfers them to the electron acceptor ubiquinone. Conclusion: Our findings indicated that various symptoms and clinical features can be found in Leigh syndrome which could be probably due to different mutations in mitochondrial genes. Therefore, appropriate clinical and laboratory settings along with brain MRI, MRS and genetic test analysis would be necessary for the early diagnosis.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Itziar Perez-Terol ◽  
Cesar Rios-Navarro ◽  
Elena de Dios ◽  
Jose M. Morales ◽  
Jose Gavara ◽  
...  

AbstractDelayed enhancement cardiovascular magnetic resonance (MR) is the gold-standard for non-invasive assessment after myocardial infarction (MI). MR microscopy (MRM) provides a level of detail comparable to the macro objective of light microscopy. We used MRM and correlative histopathology to identify infarct and remote tissue in contrast agent-free multi-sequence MRM in swine MI hearts. One control group (n = 3 swine) and two experimental MI groups were formed: 90 min of ischemia followed by 1 week (acute MI = 6 swine) or 1 month (chronic MI = 5 swine) reperfusion. Representative samples of each heart were analysed by contrast agent-free multi-sequence (T1-weighting, T2-weighting, T2*-weighting, T2-mapping, and T2*-mapping). MRM was performed in a 14-Tesla vertical axis imager (Bruker-AVANCE 600 system). Images from MRM and the corresponding histopathological stained samples revealed differences in signal intensities between infarct and remote areas in both MI groups (p-value < 0.001). The multivariable models allowed us to precisely classify regions of interest (acute MI: specificity 92% and sensitivity 80%; chronic MI: specificity 100% and sensitivity 98%). Probabilistic maps based on MRM images clearly delineated the infarcted regions. As a proof of concept, these results illustrate the potential of MRM with correlative histopathology as a platform for exploring novel contrast agent-free MR biomarkers after MI.


2011 ◽  
Vol 31 (6) ◽  
pp. 557-564 ◽  
Author(s):  
M Dogan ◽  
MG Turtay ◽  
H Oguzturk ◽  
E Samdanci ◽  
Y Turkoz ◽  
...  

Objective: The effects of electromagnetic radiation (EMR) produced by a third-generation (3G) mobile phone (MP) on rat brain tissues were investigated in terms of magnetic resonance spectroscopy (MRS), biochemistry, and histopathological evaluations. Methods: The rats were randomly assigned to two groups: Group 1 is composed of 3G-EMR-exposed rats ( n = 9) and Group 2 is the control group ( n = 9). The first group was subjected to EMR for 20 days. The control group was not exposed to EMR. Choline (Cho), creatinin (Cr), and N-acetylaspartate (NAA) levels were evaluated by MRS. Catalase (CAT) and glutathione peroxidase (GSH-Px) enzyme activities were measured by spectrophotometric method. Histopathological analyses were carried out to evaluate apoptosis in the brain tissues of both groups. Results: In MRS, NAA/Cr, Cho/Cr, and NAA/Cho ratios were not significantly different between Groups 1 and 2. Neither the oxidative stress parameters, CAT and GSH-Px, nor the number of apoptotic cells were significantly different between Groups 1 and 2. Conclusions: Usage of short-term 3G MP does not seem to have a harmful effect on rat brain tissue.


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