scholarly journals Formalin Tissue Fixation Biases Myelin-Sensitive MRI

2019 ◽  
Author(s):  
Alan C. Seifert ◽  
Melissa Umphlett ◽  
Marco Hefti ◽  
Mary Fowkes ◽  
Junqian Xu
Keyword(s):  
Signal Intensity ◽  
Relaxation Times ◽  
Formalin Fixation ◽  
Spinal Cord Tissue ◽  
Myelin Lipid ◽  
Cross Sectional ◽  
Fixed Tissue ◽  
Water Fraction ◽  
Human Spinal Cord ◽  
Induced Changes

AbstractPurposeChemical fixatives, such as formalin, form cross-links between proteins and affect the relaxation times and diffusion properties of tissue. These fixation-induced changes likely also affect myelin density measurements produced by quantitative magnetization transfer (qMT) and myelin water imaging (MWI). In this work, we evaluate these myelin-sensitive MRI methods for fixation-induced biases.MethodsWe perform qMT, MWI, and D2O-exchanged zero echo-time (ZTE) imaging on unfixed human spinal cord tissue, and repeat these measurements after 1 day and 31 days of formalin fixation.ResultsThe qMT bound pool fraction increased by 30.7±21.1% after 1 day of fixation and by 42.6±33.9% after 31 days of fixation. Myelin water fraction increased by 39.7±15.5% and 37.0±15.9% at these same time points, and mean T2 of the myelin water pool nearly doubled. Reference-normalized D2O-exchanged ZTE signal intensity increased by 8.17±6.03% after 31 days of fixation, but did not change significantly after 1 day of fixation. After fixation, specimen cross-sectional area decreased by approximately 5%; after correction for shrinkage, changes in D2O-exchanged ZTE intensity were nearly eliminated.ConclusionF and MWF are significantly increased by formalin fixation, while D2O-exchanged ZTE intensity is minimally affected. Changes in qMT and MWI may be due, in part, to delamination and formation of vacuoles in the myelin sheath. D2O-exchanged signal intensity may be altered by fixation-induced changes in myelin lipid solid-state 1H T1. We urge caution in the comparison of these measurements across subjects or specimens in different states, especially unfixed vs. fixed tissue.

White-matter relaxation time and myelin water fraction differences in young adults with autism

2014 ◽  
Vol 45 (4) ◽  
pp. 795-805 ◽  
Author(s):  
S. C. L. Deoni ◽  
J. R. Zinkstok ◽  
E. Daly ◽  
C. Ecker ◽  
S. C. R. Williams ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
Brain Connectivity ◽  
Critical Role ◽  
Relaxation Times ◽  
Imaging Study ◽  
Autism Diagnostic Observation Schedule ◽  
Cross Sectional ◽  
Water Fraction ◽  
Myelin Water Fraction

BackgroundIncreasing evidence suggests that autism is associated with abnormal white-matter (WM) anatomy and impaired brain ‘connectivity’. While myelin plays a critical role in synchronized brain communication, its aetiological role in autistic symptoms has only been indirectly addressed by WM volumetric, relaxometry and diffusion tensor imaging studies. A potentially more specific measure of myelin content, termed myelin water fraction (MWF), could provide improved sensitivity to myelin alteration in autism.MethodWe performed a cross-sectional imaging study that compared 14 individuals with autism and 14 age- and IQ-matched controls. T1 relaxation times (T1), T2 relaxation times (T2) and MWF values were compared between autistic subjects, diagnosed using the Autism Diagnostic Interview – Revised (ADI-R), with current symptoms assessed using the Autism Diagnostic Observation Schedule (ADOS) and typical healthy controls. Correlations between T1, T2 and MWF values with clinical measures [ADI-R, ADOS, and the Autism Quotient (AQ)] were also assessed.ResultsIndividuals with autism showed widespread WM T1 and MWF differences compared to typical controls. Within autistic individuals, worse current social interaction skill as measured by the ADOS was related to reduced MWF although not T1. No significant differences or correlations with symptoms were observed with respect to T2.ConclusionsAutistic individuals have significantly lower global MWF and higher T1, suggesting widespread alteration in tissue microstructure and biochemistry. Areas of difference, including thalamic projections, cerebellum and cingulum, have previously been implicated in the disorder; however, this is the first study to specifically indicate myelin alteration in these regions.

Mechanical thumb pain in a systemic sclerosis patient: simple first carpometacarpal osteoarthritis?

Rheumatology ◽  
2021 ◽  
Author(s):  
Guillaume LARID ◽  
Pier-Olivier DUBOE ◽  
Jean-Denis LAREDO ◽  
Elisabeth GERVAIS
Keyword(s):  
Systemic Sclerosis ◽  
Signal Intensity ◽  
Topoisomerase I ◽  
Joint Space ◽  
Carpometacarpal Joint ◽  
Cross Sectional ◽  
First Carpometacarpal Joint ◽  
Provide Pain Relief ◽  
Long Time ◽  
Carpometacarpal Osteoarthritis

Abstract A 70-year-old female patient treated with methotrexate for diffuse cutaneous systemic sclerosis (SSc) came up with mechanical pain over the left thumb for several months. SSc was diagnosed based on a clinical picture associating puffy fingers, skin sclerosis, wrist arthralgia, pulmonary hypertension, presence of antinuclear factors and antibodies against Topoisomerase-I. Her complaint was attributed to first carpometacarpal joint osteoarthritis and treated with orthesis, which did not provide pain relief after 5 months of regular use. Hand radiograph showed first carpometacarpal arthropathy with joint space narrowing and marked sclerosis of the first proximal metacarpal (A). MRI showed an area of very low signal intensity on T1- and T2-weighted images (B) within the proximal metacarpal, distal trapezium and medial joint recess surrounded by bone marrow edema. Mild peripheral enhancement was present after gadolinium injection. CT-scan (C) showed that the low signal intensity material visible at MRI consisted of calcium. These aspects are suggestive of scleroderma arthropathy rather than common first carpometacarpal osteoarthritis. Though involvement of the first carpometacarpal joint is long time known in SSc [1], it remains exceptional when looking at cross-sectional studies [2]. Carefully analyzing imaging exams is the key point in order not to miss this rare scleroderma feature.

Musculoskeletal MRI Findings of Haematological Diseases

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Sameh Mohammed Abdelwahab ◽  
Hazem Ibrahim Abdelrahman ◽  
Pola Ibrahim Said
Keyword(s):  
Bone Marrow ◽  
Signal Intensity ◽  
Cross Sectional Study ◽  
Mr Images ◽  
University Hospitals ◽  
Mri Findings ◽  
Cross Sectional ◽  
Hematological Diseases ◽  
Musculoskeletal Mri ◽  
Normal Composition

Abstract Background Hematologic diseases are a group of prevalent and clinically diverse diseases that can affect any organ system. Hematologic disorders frequently involve bone and associated tissues causing significant alterations in the bone marrow and may have relevant side effects on the skeleton. In order to evaluate findings in bone marrow on MR imaging, it is essential to understand the normal composition and distribution of bone marrow and the changes in marrow that occur with age, as well as the basis for the MR signals from marrow and the factors that affect those signals. Aim of the Work To describe the musculoskeletal MRI findings in patients with hematological diseases. Patients and Methods cross sectional study was conducted in Ain Shams University hospitals on patients confirmed with hematological disease undergoing musculoskeletal MRI. Conclusion Magnetic resonance imaging is very beneficial noninvasive modality to evaluate bone marrow and detecting marrow lesions due to its ability to provide information at the level of cellular and chemical composition. Knowing normal marrow components and composition and their variation, as well as of factors that affect MR signal intensity, is important for optimal interpretation of MR images. The signal intensity, morphology, and location of marrow findings on MRI can be used to provide accurate diagnoses and to guide treatment of the discussed hematological diseases.

MR fingerprinting enables quantitative measures of brain tissue relaxation times and myelin water fraction in the first five years of life

NeuroImage ◽  
2019 ◽  
Vol 186 ◽  
pp. 782-793 ◽  
Author(s):  
Yong Chen ◽  
Meng-Hsiang Chen ◽  
Kristine R. Baluyot ◽  
Taylor M. Potts ◽  
Jordan Jimenez ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Relaxation Times ◽  
Water Fraction ◽  
Myelin Water Fraction ◽  
Tissue Relaxation

scholarly journals Influence of prolonged formalin fixation of tissue samples on the sensitivity of chromogenic in situ hybridization

2011 ◽  
Vol 23 (6) ◽  
pp. 1212-1216 ◽  
Author(s):  
Meike M. Mostegl ◽  
Barbara Richter ◽  
Nora Dinhopl ◽  
Herbert Weissenböck
Keyword(s):  
In Situ Hybridization ◽  
Nucleic Acid ◽  
Signal Intensity ◽  
Formalin Fixation ◽  
Proteinase K ◽  
Cross Linking ◽  
Fixation Time ◽  
Tissue Samples ◽  
Chromogenic In Situ Hybridization

Chromogenic in situ hybridization (ISH) is a commonly used tool in diagnostic pathology to detect pathogens in formalin-fixed, paraffin-embedded (FFPE) tissue sections. Prolonged formalin fixation time was identified to be a limiting factor for the successful detection of nucleic acid from different pathogens, most probably due to the cross-linking activity of formalin between RNA, DNA, and proteins. Therefore, in the current study, the influence of formalin fixation time on ISH signal intensity of 2 viral ( Porcine circovirus-2 [PCV-2] and Porcine respiratory and reproductive virus [PRRSV]) and 2 protozoal agents ( Cryptosporidium serpentis and Tritrichomonas sp.) was evaluated. Tissue samples were fixed in 7% neutral buffered formaldehyde solution, and at defined intervals, pieces were embedded in paraffin wax and subjected to pathogen-specific ISH. For all 4 pathogens, the signal intensity remained comparable with the starting ISH signal for different periods of fixation (PCV-2: 6 weeks, PRRSV: 23 weeks, C. serpentis: 55 weeks, Tritrichomonas sp.: 53 weeks). Thereafter, the signal started to decline until loss of nucleic acid detection. The influence of increased proteinase K concentrations for inverting the formalin-induced cross-linking activity was examined compared with the standard protocol. With all 4 infectious agents, a 4-fold proteinase K concentration restored the ISH signals to a level comparable with 1 day of fixation. In conclusion, the influence of prolonged formalin fixation on the intensity of detected ISH signal highly depends on the analyzed infectious agent and the pretreatment protocol.

Radiation-induced Changes in MR Signal Intensity and Contrast Enhancement of Lumbosacral Vertebrae: Do Changes Occur Only Inside the Radiation Therapy Field?

Radiology ◽  
2002 ◽  
Vol 222 (1) ◽  
pp. 179-183 ◽  
Author(s):  
Shoichiro Otake ◽  
Nina A. Mayr ◽  
Toshihiro Ueda ◽  
Vincent A. Magnotta ◽  
William T. C. Yuh
Keyword(s):  
Radiation Therapy ◽  
Contrast Enhancement ◽  
Signal Intensity ◽  
Radiation Induced ◽  
Therapy Field ◽  
Induced Changes

Mechanisms leading to restoration of muscle size with exercise and transplantation after spinal cord injury

2000 ◽  
Vol 279 (6) ◽  
pp. C1677-C1684 ◽  
Author(s):  
Esther E. Dupont-Versteegden ◽  
René J. L. Murphy ◽  
John D. Houlé ◽  
Cathy M. Gurley ◽  
Charlotte A. Peterson
Keyword(s):  
Spinal Cord ◽  
Satellite Cell ◽  
Fiber Type ◽  
Cell Activity ◽  
Muscle Size ◽  
Spinal Cord Tissue ◽  
Cellular Mechanisms ◽  
Cross Sectional ◽  
Cord Injury ◽  
Nuclear Number

We have shown that cycling exercise combined with fetal spinal cord transplantation restored muscle mass reduced as a result of complete transection of the spinal cord. In this study, mechanisms whereby this combined intervention increased the size of atrophied soleus and plantaris muscles were investigated. Rats were divided into five groups ( n = 4, per group): control, nontransected; spinal cord transected at T10 for 8 wk (Tx); spinal cord transected for 8 wk and exercised for the last 4 wk (TxEx); spinal cord transected for 8 wk with transplantation of fetal spinal cord tissue into the lesion site 4 wk prior to death (TxTp); and spinal cord transected for 8 wk, exercised for the last 4 wk combined with transplantation 4 wk prior to death (TxExTp). Tx soleus and plantaris muscles were decreased in size compared with control. Exercise and transplantation alone did not restore muscle size in soleus, but exercise alone minimized atrophy in plantaris. However, the combination of exercise and transplantation resulted in a significant increase in muscle size in soleus and plantaris compared with transection alone. Furthermore, myofiber nuclear number of soleus was decreased by 40% in Tx and was not affected in TxEx or TxTp but was restored in TxExTp. A strong correlation ( r = 0.85) between myofiber cross-sectional area and myofiber nuclear number was observed in soleus, but not in plantaris muscle, in which myonuclear number did not change with any of the experimental manipulations. 5′-Bromo-2′-deoxyuridine-positive nuclei inside the myofiber membrane were observed in TxExTp soleus muscles, indicating that satellite cells had divided and subsequently fused into myofibers, contributing to the increase in myonuclear number. The increase in satellite cell activity did not appear to be controlled by the insulin-like growth factors (IGF), as IGF-I and IGF-II mRNA abundance was decreased in Tx soleus and plantaris, and was not restored with the interventions. These results indicate that, following a relatively long postinjury interval, exercise and transplantation combined restore muscle size. Satellite cell fusion and restoration of myofiber nuclear number contributed to increased muscle size in the soleus, but not in plantaris, suggesting that cellular mechanisms regulating muscle size differ between muscles with different fiber type composition.

scholarly journals ACL Size, but Not Signal Intensity, Is Influenced by Sex, Body Size, and Knee Anatomy

2021 ◽  
Vol 9 (12) ◽  
pp. 232596712110638
Author(s):  
Samuel C. Barnett ◽  
Martha M. Murray ◽  
Sean W. Flannery ◽  
Danilo Menghini ◽  
Braden C. Fleming ◽  
...  
Keyword(s):  
Signal Intensity ◽  
Tibial Slope ◽  
Cross Sectional Area ◽  
Intercondylar Notch ◽  
Activity Levels ◽  
Sectional Area ◽  
Tissue Quality ◽  
Cross Sectional ◽  
Notch Width ◽  
Intercondylar Notch Width

Background: Little is known about sex-based differences in anterior cruciate ligament (ACL) tissue quality in vivo or the association of ACL size (ie, volume) and tissue quality (ie, normalized signal intensity on magnetic resonance imaging [MRI]) with knee anatomy. Hypothesis: We hypothesized that (1) women have smaller ACLs and greater ACL normalized signal intensity compared with men, and (2) ACL size and normalized signal intensity are associated with age, activity levels, body mass index (BMI), bicondylar width, intercondylar notch width, and posterior slope of the lateral tibial plateau. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Knee MRI scans of 108 unique ACL-intact knees (19.7 ± 5.5 years, 62 women) were used to quantify the ACL signal intensity (normalized to cortical bone), ligament volume, mean cross-sectional area, and length. Independent t tests were used to compare the MRI-based ACL parameters between sexes. Univariate and multivariate linear regression analyses were used to investigate the associations between normalized signal intensity and size with age, activity levels, BMI, bicondylar width, notch width, and posterior slope of the lateral tibial plateau. Results: Compared with men, women had significantly smaller mean ACL volume (men vs women: 2028 ± 472 vs 1591 ± 405 mm3), cross-sectional area (49.4 ± 9.6 vs 41.5 ± 8.6 mm2), and length (40.8 ± 2.8 vs 38.1 ± 3.1 mm) ( P < .001 for all), even after adjusting for BMI and bicondylar width. There was no difference in MRI signal intensity between men and women (1.15 ± 0.24 vs 1.12 ± 0.24, respectively; P = .555). BMI, bicondylar width, and intercondylar notch width were independently associated with a larger ACL ( R 2 > 0.16, P < .001). Younger age and steeper lateral tibial slope were independently associated with shorter ACL length ( R 2 > 0.03, P < .04). The combination of BMI and bicondylar width was predictive of ACL volume and mean cross-sectional area ( R 2 < 0.3). The combination of BMI, bicondylar width, and lateral tibial slope was predictive of ACL length ( R 2 = 0.39). Neither quantified patient characteristics nor anatomic variables were associated with signal intensity. Conclusion: Men had larger ACLs compared with women even after adjusting for BMI and knee size (bicondylar width). No sex difference was observed in signal intensity, suggesting no difference in tissue quality. The association of the intercondylar notch width and lateral tibial slope with ACL size suggests that the influence of these anatomic features on ACL injury risk may be partially explained by their effect on ACL size. Registration: NCT02292004 and NCT02664545 ( ClinicalTrials.gov identifier).

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