Age-related changes in the pediatric brain: proton T1 in healthy children and in children with sickle cell disease

The goal of this study was to characterize the expected range of variation in T1 (spin-lattice relaxation time) of brain tissue in vivo, as a function of age, and to use these maturational norms to study children with sickle cell disease (SCD). A well-validated method (TurboPAIR) was used to measure T1 in 10 tissues in a study group of 200 healthy subjects (ages 4.5 to 79.3; 101 male and 99 female), in a transverse slice at the level of the basal ganglia. Brain T1 was significantly related to age in every tissue characterized (p < 0.001), including the splenium (p < 0.01). Quantitative MRI suggests that brain T1 continues to change throughout the lifespan of healthy subjects free of neurologic complaints. Age-related changes follow a different schedule in each tissue, and age is a stronger determinant of T1 in gray matter than in white matter. Analysis of 141 patients with SCD shows that patients have lower T1 than normal, in both the caudate and the cortex (p < 0.001).     

Brain imaging: Comparison of T1W FLAIR BLADE with conventional T1W SE

IntroductionAlthough T1 weighted spin echo (T1W SE) images are widely used to study anatomical details and pathologic abnormalities of the brain, its role in delineation of lesions and reduction of artifacts has not been thoroughly investigated. BLADE is a fairly new technique that has been reported to reduce motion artifacts and improve image quality.ObjectiveThe primary objective of this study is to compare the quality of T1-weighted fluid attenuated inversion recovery (FLAIR) images with BLADE technique (T1W FLAIR BLADE) and the quality of T1W SE images in the MR imaging of the brain. The goal is to highlight the advantages of the two sequences as well as which one can better reduce flow and motion artifacts so that the imaging of the lesions will not be impaired.Materials and methodsBrain examinations with T1W FLAIR BLADE and T1W SE sequences were performed on 48 patients using a 1.5 T scanner. These techniques were evaluated by two radiologists based on: a) a qualitative analysis i.e. overall image quality, presence of artifacts, CSF nulling; and b) a quantitative analysis of signal-to-noise ratios (SNR), contrast-to-noise ratios (CNR) and Relative Contrast. The statistical analysis was performed using the Kruskal-Wallis non-parametric system.ResultsIn the qualitative analysis, BLADE sequences had a higher scoring than the conventional sequences in all the cases. The overall image quality was better on T1W FLAIR BLADE. Motion and flow-related artifacts were lower in T1W FLAIR BLADE. Regarding the SNR measurements, T1W SE appeared to have higher values in the majority of cases, whilst T1W-FLAIR BLADE had higher values in the CNR and Relative Contrast measurements.ConclusionT1W FLAIR BLADE sequence appears to be superior to T1W SE in overall image quality and reduction of motion and flow-pulsation artifacts as well as in nulling CSF and has been preferred by the clinicians. T1W FLAIR BLADE may be an alternative approach in brain MRI imaging.     

Sex-dependent gene expression in early brain development of chicken embryos

Background  

Differentiation of the brain during development leads to sexually dimorphic adult reproductive behavior and other neural sex dimorphisms. Genetic mechanisms independent of steroid hormones produced by the gonads have recently been suggested to partly explain these dimorphisms.     

Myelin characterization of fetal brain with mono-point estimated T1-maps

Magnetic resonance imaging (MRI) allows non-invasive assessment of fetus brain maturation at the beginning of the third trimester because of its high sensitivity for fat and water content changes accompanying the myelin formation. In this article we propose a new ultra-fast mono point T(1)-map method based on simplified optimized Gradient Echo (GE) two-point method. Results are compared between the two methods and the precision discussed. This quantitative method can be used in clinical routine, as sedation is not needed for patients.     

Proton magnetic resonance spectroscopy of brain lesions in children with neurofibromatosis type 1.

Two of the recognized cranial MRI findings in children with neurofibromatosis type 1 (NF1) are neurofibromatosis bright objects (NBO) and brain glioma. Their differential diagnosis can be problematic. This study aimed to determine the features of these abnormalities on short echo-time in-vivo proton magnetic resonance spectroscopy. Twenty children under the age of 16 with NF1 were studied. A single voxel, short echo-time technique (TE = 20 ms; TR = 5000 ms) was used to obtain proton spectra of typical NBO and any regions suggestive of atypical bright objects or tumor. Nine children without neurofibromatosis with no structural brain abnormality acted as aged-matched comparisons. A semi-quantitative analysis indicated significant increase in choline and myo-inisitol in tumors compared to typical NBO (p < 0.05) and compared to controls (p < 0.05); reduction in the levels of N-acetyl moieties in NBO compared to controls (p < 0.05); reduction in N-acetyl in tumors compared to controls (p < 0.001); and reduction in glutamate/glutamine in tumors compared to controls (p < 0.05). This cross-sectional data suggests that proton spectroscopy can aid differentiating between NBO and brain (non-optic/hypothalamic) glioma. Typical NBO have different short echo-time spectroscopic appearances compared to normal brain.     

Marrow infarction in sickle cell anemia: correlation with marrow type and distribution by MRI

Ischemic necrosis of bone is believed to occur exclusively in areas of predominantly fatty marrow. Sickle cell disease is unusual in that marrow infarction occurs in areas of active hematopoiesis. MR images of long bone obtained in ten patients with sickle cell anemia (SCA) were analyzed to correlate the distribution and appearance of marrow infarction with the type of marrow. While the hematopoietic marrow predominated in metaphyseal and diaphyseal regions of femurs and tibias, the fatty or mixed marrow was the most common pattern in epiphyses. Infarcts occurred in fatty as well as hematopoietic marrow. Marrow infarcts were isointense or minimally hyperintense on T1 weighted images with the hematopoietic marrow and therefore difficult to detect. On T2 weighted images, the infarcts showed very high signal. T2 weighted images are essential for detection of marrow infarction. Soft tissue changes seen as low signal on T1 and high signal on T2, may be secondary to intramuscular injections of analgesics or muscle ischemia occurring during sickle crisis.     

The development of acoustic cues to coda contrasts in young children learning American English

Research on children's speech perception and production suggests that consonant voicing and place contrasts may be acquired early in life, at least in word-onset position. However, little is known about the development of the acoustic correlates of later-acquired, word-final coda contrasts. This is of particular interest in languages like English where many grammatical morphemes are realized as codas. This study therefore examined how various non-spectral acoustic cues vary as a function of stop coda voicing (voiced vs. voiceless) and place (alveolar vs. velar) in the spontaneous speech of 6 American-English-speaking mother-child dyads. The results indicate that children as young as 1;6 exhibited many adult-like acoustic cues to voicing and place contrasts, including longer vowels and more frequent use of voice bar with voiced codas, and a greater number of bursts and longer post-release noise for velar codas. However, 1;6-year-olds overall exhibited longer durations and more frequent occurrence of these cues compared to mothers, with decreasing values by 2;6. Thus, English-speaking 1;6-year-olds already exhibit adult-like use of some of the cues to coda voicing and place, though implementation is not yet fully adult-like. Physiological and contextual correlates of these findings are discussed.     

Chromatin supraorganization, mitotic abnormalities and proliferation in cells with increased or down-regulated lox expression: Indirect evidence of a LOX-histone H1 interaction in vivo

Lysyl oxidases (LOXs) are enzymes that permit the covalent crosslinking of the component chains of collagen and elastin. These enzymes are present inside the nuclei of certain mammalian cells. Previous studies have proposed LOX binding to histone H1 in vitro, and histone H1 is known to control global chromatin compaction and mitotic chromosome architecture. Therefore, in the present study, we analyzed chromatin supraorganizational changes, mitotic abnormalities, mitotic indices and cell death ratios in COS-7 and NRK-49F cells with high and low lox expression levels, respectively. The objective was to support biochemical data of LOX-H1 interaction, by providing evidence of chromatin remodeling in vivo, under different lox expressions. Chromatin decondensation assessed by image analysis was observed in COS-7 cells with increased lox expression. This decondensation is suggested to be promoted by LOX actions on histone H1, which loosens the DNA-H1 complex. In NRK-49F cells transfected with antisense lox or subjected to treatment with beta-aminopropionitrile (BAPN), chromatin condensation and nuclear phenotypic variability were found, which may be due to reduced LOX-H1 interaction. When lox expression was increased in COS-7 cells, the frequency of irregular chromosome plates was not affected, but cell proliferation decreased and "cell death preceded by multinucleation" increased. In NRK-49F cells there was accelerated proliferation induced by transfection with the antisense lox, and confirmed when cells were treated with BAPN. Apoptosis increased in NRK-49F cells only with BAPN treatment whereas cell death preceded by multinucleation increased only after antisense lox transfection. The data presented herein regarding chromatin remodeling indirectly support the hypothesis that LOX binds to histone H1 in vivo. Cell proliferation in COS-7 and NRK-49F cells and cell death at least in COS-7 cells agree with predicted effects of LOX interference in these processes.     

In vivo evaluation of the reproducibility of T1 and T2 measured in the brain of patients with multiple sclerosis.

The precision (reproducibility) of relaxation times derived from magnetic resonance images of patients with multiple sclerosis (MS) were investigated. Measurements of 10 MS patients were performed at 1.5 T on two occasions within 1 wk. T1 and T2 was measured using a partial saturation inversion recovery sequence (6 points) and a Carr-Purcell-Meiboom-Gill phase alternating-phase shift multiple spin-echo sequence with 32 echoes. Regions of interest (ROI) were placed both in apparently normal white matter and plaques. The precision (+/- 1.96 SD) and the confidence intervals for T1 and T2 for white matter and plaques were calculated. The precision of T1 for white matter and plaques was respectively +/- 94 msec and +/- 208 msec. The precision of T2 for white matter and plaques was respectively +/- 18 msec and +/- 26 msec. For all measurements the coefficient of variation was about 9%. Judging from our own study and others as well, a precision better than 10% for T1 and T2 would seem unrealistic at present.     

Effect of hepatic steatosis on native T1 mapping of 3T magnetic resonance imaging in the assessment of T1 values for patients with non-alcoholic fatty liver disease

PurposeThis study investigated whether T1 values in native T1 mapping of 3T magnetic resonance imaging (MRI) of the liver were affected by the fatty component.MethodsThis prospective study involved 340 participants from a population-based cohort study between May 8, 2018 and August 8, 2019. Data obtained included: (1) hepatic stiffness according to magnetic resonance elastography (MRE); (2) T1 value according to T1 mapping; (3) fat fraction and iron concentration from multi-echo Dixon; and (4) clinical indices of hepatic steatosis including body mass index, waist circumference, history of diabetes, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, and triglycerides. The correlations between T1 value and fat fraction, and between T1 value and liver stiffness were assessed using Pearson's correlation coefficient. The independent two-sample t-test was used to evaluate the differences in T1 values according to the presence or absence of hepatic steatosis, and the one-way analysis of variance was used to evaluate the difference in T1 value by grading of hepatic steatosis according to MRI-based proton density fat fraction (PDFF). In addition, univariate and multivariate linear regression analyses were performed to determine whether other variables influenced the T1 value.ResultsT1 value showed a positive correlation with the fat fraction obtained from PDFF (r = 0.615, P < 0.001) and with the liver stiffness obtained from MRE (r = 0.370, P < 0.001). Regardless of the evaluation method, the T1 value was significantly increased in subjects with hepatic steatosis (P < 0.001). When comparing hepatic steatosis grades based on MRI-PDFF, the mean T1 values were significantly different in all grades, and the T1 value tended to increase as the grade increased (P < 0.001, P for trend <0.001). On multiple linear regression analysis, the T1 value was influenced by MRI-PDFF, calculated liver iron concentration, liver stiffness, and serum aspartate aminotransferase level.ConclusionThe T1 value obtained by current T1 mapping of 3T MRI was affected by the liver fat component and several other factors such as liver stiffness, iron concentration, and inflammation.     

An approach for computer-aided detection of brain metastases in post-Gd T1-W MRI

Purpose

To develop an approach for computer-aided detection (CAD) of small brain metastases in post-Gd T1-weighted magnetic resonance imaging (MRI).

Method

A set of unevenly spaced 3D spherical shell templates was optimized to localize brain metastatic lesions by cross-correlation analysis with MRI. Theoretical and simulation analyses of effects of lesion size and shape heterogeneity were performed to optimize the number and size of the templates and the cross-correlation thresholds. Also, effects of image factors of noise and intensity variation on the performance of the CAD system were investigated. A nodule enhancement strategy to improve sensitivity of the system and a set of criteria based upon the size, shape and brightness of lesions were used to reduce false positives. An optimal set of parameters from the FROC curves was selected from a training dataset, and then the system was evaluated on a testing dataset including 186 lesions from 2753 MRI slices. Reading results from two radiologists are also included.

Results

Overall, a 93.5% sensitivity with 0.024 of intra-cranial false positive rate (IC-FPR) was achieved in the testing dataset. Our investigation indicated that nodule enhancement was very effective in improving both sensitivity and specificity. The size and shape criteria reduced the IC-FPR from 0.075 to 0.021, and the brightness criterion decreases the extra-cranial FPR from 0.477 to 0.083 in the training dataset. Readings from the two radiologists had sensitivities of 60% and 67% in the training dataset and 70% and 80% in the testing dataset for the metastatic lesions <5 mm in diameter.

Conclusion

Our proposed CAD system has high sensitivity and fairly low FPR for detection of the small brain metastatic lesions in MRI compared to the previous work and readings of neuroradiologists. The potential of this method for assisting clinical decision- making warrants further evaluation and improvements.     

Considerations in applying 3D PRESS H-1 brain MRSI with an eight-channel phased-array coil at 3 T

The purpose of this study was to assess the benefits of a 3 T scanner and an eight-channel phased-array head coil for acquiring three-dimensional PRESS (Point REsolved Spectral Selection) proton (H-1) magnetic resonance spectroscopic imaging (MRSI) data from the brains of volunteers and patients with brain tumors relative to previous studies that used a 1.5 T scanner and a quadrature head coil. Issues that were of concern included differences in chemical shift artifacts, line broadening due to increased susceptibility at higher field strengths, changes in relaxation times and the increased complexity of the postprocessing software due to the need for combining signals from the multichannel data. Simulated and phantom spectra showed that very selective suppression pulses with a thickness of 40 mm and an overpress factor of at least 1.2 are needed to reduce chemical shift artifact and lipid contamination at higher field strengths. Spectral data from a phantom and those from six volunteers demonstrated that the signal-to-noise ratio (SNR) in the eight-channel coil was more than 50% higher than that in the quadrature head coil. For healthy volunteers and eight patients with brain tumors, the SNR at 3 T with the eight-channel coil was on average 1.5 times higher relative to the eight-channel coil at 1.5 T in voxels from normal-appearing brains. In combination with the effect of a higher field strength, the use of the eight-channel coil was able to provide an increase in the SNR of more than 2.33 times the corresponding acquisition at 1.5 T with a quadrature head coil. This is expected to be critical for clinical applications of MRSI in patients with brain tumors because it can be used to either decrease acquisition time or improve spatial resolution.     

Complementary use of T2-weighted and postcontrast T1- and T21-weighted imaging to distinguish sites of reversible and irreversible brain damage in focal ischemic lesions in the rat brain

The evolution of a photochemically induced cortical infarct was monitored using T₂-, postcontrast (GdDOTA) T₁-, and postcontrast (DyDTPA-BMA) T₂¹-weighted NMR imaging techniques. Data acquired with these different NMR imaging types were compared, both qualitatively and quantitatively. The T₂¹-weighted NMR images after sprodiamide injection (DyDTPA-BMA) were perfusion-weighted images that allowed the differentiation between several infarct-related areas in terms of different degrees of perfusion deficiency. No quantitative information on cerebral blood flow (CBF) was obtained. A clear distinction was made between areas with a complete lack of CBF located in the core of the lesion and temporary CBF insufficiencies in the rim surrounding this core. Concomitant observations on T₂-weighted and postcontrast T₁-weighted images revealed the same temporary rim characterized by an increased water content, and an intact blood-brain barrier (BBB), as well as by reduced perfusion. This rim appeared within the first hours after infarct induction, reached a maximum 24 h later, and lasted between 3–5 days, when its size gradually decreased until complete disappearance. These observations suggest the existence of an area at risk. Only on postcontrast T₁-weighted images, the core of the lesion remained visible during the whole experimental period (10 days) and reflected in all likelihood the irreversibly damaged ischemic central core. The combined application of different NMR imaging techniques when studying focal cerebral infarctions in the rat brain allowed us to distinguish, in terms of NMR characteristics, zones of reversible from irreversible brain damage and to estimate the severity of the damage. This might offer an appropriate experimental setup for the screening of cerebroprotective compounds.     

Comparison of T1-weighted spin-echo and 3D T1-weighted multi-shot Echo Planar pulse sequences in imaging the brain at it.

The purpose of this study was to evaluate the ability of three dimensional T1-weighted multi-shot Echo Planar Imaging (3D T1w EPI) MR pulse sequence to provide comparable to T1w Spin Echo (SE) results in various diseases of the brain, during shorter acquisition times. Thirty-six patients (aged 30-74 years) with various indications were included in the study. All examinations were performed with a 1T MR scanner with a maximum gradient strength of 15 mT/m. The SE sequence lasted 3 min 50s and the 3D T1w EPI 59s. The quantitative analysis included number of enhancing lesions, signal-to-noise ratio of the enhancing lesions and contrast-to-noise ratio (CNR) between enhancing lesions and white matter in both sequences before and after i.v. administration of 0.1 mmol/kg gadopentetate dimeglumine. In addition, the percentage increase of enhancement was measured in each lesion of each sequence. The qualitative analysis included a) conspicuity of the lesions and b) presence of artifacts. The T1w SE sequence was significantly better compared to 3D T1w EPI in all quantitative measurements with the exception of CNR of enhancing lesions before contrast administration and the percentage enhancement. The conspicuity of the lesions did not differ between the two sequences. The EPI sequence presented with significantly more artifacts. We conclude that the 3D T1w EPI sequence could not be used instead of the conventional T1w SE, in routine imaging of the brain. Its overall diagnostic capability, could be useful only in uncooperative patients.     

BRAHMA: Population specific T1, T2, and FLAIR weighted brain templates and their impact in structural and functional imaging studies

Differences in brain morphology across population groups necessitate creation of population-specific Magnetic Resonance Imaging (MRI) brain templates for interpretation of neuroimaging data. Variations in the neuroanatomy in a genetically heterogeneous population make the development of a population-specific brain template for the Indian subcontinent imperative. A dataset of high-resolution 3D T1, T2-weighted, and FLAIR images acquired from a group of 113 volunteers (M/F - 56/57, mean age-28.96 ± 7.80 years) are used to construct T1, T2-weighted, and FLAIR templates, collectively referred to as Indian Brain Template, “BRAHMA”. A processing pipeline is developed and implemented in a MATLAB based toolbox for template construction and generation of tissue probability maps and segmentation atlases, with additional labels for deep brain regions such as the Substantia Nigra generated from the T2-weighted and FLAIR templates. The use of BRAHMA template for analysis of structural and functional neuroimaging data obtained from Indian participants, provides improved accuracy with statistically significant results over that obtained using the ICBM-152 (International Consortium for Brain Mapping) template. Our results indicate that segmentations generated on structural images are closer in volume to those obtained from registration to the BRAHMA template than to the ICBM-152. Furthermore, functional MRI data obtained for Working Memory and Finger Tapping paradigms processed using the BRAHMA template show a significantly higher percentage of the activation area than ICBM-152 in relevant brain regions, i.e. the left middle frontal gyrus, and the left and right precentral gyri, respectively. The availability of different image contrasts, tissue maps, and segmentation atlases makes the BRAHMA template a comprehensive tool for multi-modal image analysis in laboratory and clinical settings.     

In vivo NMR imaging and T1 measurements of water protons in the human brain

Nuclear magnetic resonance (NMR) proton density images of the human brain have been made by the FONAR method. Spin-lattice relaxation times, T₁, of water hydrogen protons have been determined at random positions within frontal and temporal regions of the human brain. The primary purpose of this ongoing research is to accumulate a large data base of normal T₁ values for water protons in normal human brain tissue. Our experience to data includes 31 measurements on 18 volunteer subjects, and the mean value ± standard deviation is 215 ± 42 msec. In addition, two metastatic lesions of the brain were studied and found to have T₁ values longer than those for normal brain tissue.     

Combined volumetric T1, T2 and secular-T2 quantitative MRI of the brain: age-related global changes (preliminary results)

The combined T1, T2 and secular-T2 pixel frequency distributions of 24 adult human brains were studied in vivo using a technique based on the mixed-TSE pulse sequence, dual-space clustering segmentation and histogram gaussian decomposition. Pixel frequency histograms of whole brains and the four principal brain compartments were studied comparatively and as function of age. For white matter, the position of the T1 peak correlates with age (R2 =.7868) when data are fitted to a quadratic polynomial. For gray matter, a weaker age correlation is found (R2 =.3687). T2 and secular-T2 results are indicative of a weaker correlation with age. The technique and preliminary results presented herein may be useful for characterizing normal as well as abnormal aging of the brain, and also for comparison with the results obtained with alternative quantitative MRI methodologies.     

T1 and proton density at 7 T in patients with multiple sclerosis: an initial study

Magnetic resonance imaging of cortical lesions due to multiple sclerosis (MS) has been hampered by the lesions' small size and low contrast to adjacent, normal-appearing tissue. Knowing cortical lesion T1 and proton density (PD) would be highly beneficial for the process of developing and optimizing dedicated magnetic resonance (MR) sequences through computer modeling of MR tissue responses. Eight patients and seven healthy control subjects were scanned at 7 T using a series of inversion recovery turbo field echo scans with varying inversion times. Regions of interest were drawn in white matter, gray matter, cortical lesions, white matter lesions and cerebrospinal fluid. White matter and gray matter T1s were significantly higher in MS patients than in controls. Cortical and white matter lesion T1 and PD are also presented for the first time. The advantages of ultrahigh field MR imaging will be important for future investigations in MS research and sequence optimization for the detection of cortical lesions.     

The effect of Gd-DTPA on T(1)-weighted choline signal in human brain tumours

The influence of Gd-DTPA on T(1)-weighted (T(1)W) proton MR spectra has been investigated in 19 patients with histologically verified low (n = 13) or high-grade (n = 6) gliomas. Repeat measurements were performed on 9 patients (7 low-grade and 2 high-grade), with 28 examinations performed in total. Comparison of spectra obtained before and after 0.2 mmol/kg Gd-DTPA showed contrast agent induced broadening of the choline signal without significant signal area change. Lack of enhancement of the choline signal with the T(1)-weighted acquisitions implies that the contrast agent and the trimethylamine-containing species do not undergo significant direct interaction. Contrast agent induced changes in the choline signal observed in this and previous studies may, therefore, be attributable to T2*/susceptibility-based effects.     

Assessment of T1 time course changes and tissue-blood ratios after Gd-DTPA administration in brain tumors

Sequential T1 changes in brain tumor tissue after Gd-DTPA administration were investigated in 10 patients, including 4 meningiomas, 2 gliomas, 3 metastatic cerebral tumors and 1 brain abscess. T1 values were measured serially for 60 minutes following Gd-DTPA injection using a magnetic focusing technique. In vitro T1 of the whole blood samples was also comparatively examined. Time processes in the tissue-blood ratio (TBR) were calculated from two-point relaxation rates at 5 and 30 minutes. The obtained ratios of TBR were ranged from 1.0 to 3.0, probably depending on histological types of brain tumor (the value of 1.0 to 1.5 for meningioma and 1.5 to 3.0 for glioma and metastatic tumor). No significant changes in the T1 value were observed in the examined normal tissue and peritumoral edema. These results indicate that Gd-DTPA plays an important role not only as an image enhancer for tumor tissue but also as an indicator for estimating the blood-brain barrier function.