Diffusion Tensor MRI of Brain in Healthy Adult Population: Normative Fractional Anisotropy Values at 3 Tesla MRI
Correspondence Address :
Dr. Deepakkumar V Mehta,
Professor, Department of Radiodiagnosis, Pramukhswami Medical College and Shree Krishna Hospital, Bhaikaka University, Gokal Nagar, Karamsad-388325, District Anand, Gujarat, India.
E-mail: firstname.lastname@example.org; email@example.com
Introduction: Diffusion Tensor Imaging (DTI) technique and its clinical application are increasing in clinical routine practice, still very less normative data is available. Awareness regarding regional differences in Fractional Anisotropy (FA) measurements is very important when routinely DTI is used in clinical Magnetic Resonance Imaging (MRI).
Aim: To determine the normative FA values data at 3 Tesla (3T) MRI and to determine the degradation of FA values in various regions of brain values with age.
Materials and Methods: This cross-sectional study involved a total of 52 participants without any abnormal findings ( presence of tumour, stroke, infarct, degeneration, etc) and whose brain scanning was performed at 3T MRI, in the Department of Radiodiagnosis, Shree Krishna Hospital, and Pramukhswami Medical College, Karamsad, Anand, Gujarat, India. A DTI protocol was set for the healthy patient’s brain scanning. The colour-coded DTI brain images were postprocessed carefully to draw a circular Region of Interest (ROI) in the required areas of white matter and FA values were noted. Descriptive statistics were used to find out the normative data in 11 regions of the brain on right and left side. Pearson correlation was used to check the correlation of FA values with age.
Results: There were 52 patients in the present study, with a male to female ratio of 1.7:1 and a mean age of 52 years. The highest FA values were observed in the splenium (0.809), genu (0.767), the body of the corpus callosum (0.627), and the posterior limb of the internal capsule (0.721), rest areas showed moderate to low FA values. Pearson correlation was used to find the variation in the FA values with age in three age groups 18-40, 41-60 and >60 years, where moderate changes in FA values with age were seen in a few regions of the brain such as genu (right side) with p-value=0.003 and foramen magnum at CVJ level (right side) with a p-value of 0.001.
Conclusion: Generally, FA values intend to change with the presence of multiple tract areas, field strength, coil sensitivity, and partial volume averaging. FA values were also found to be affected with respect to increasing age.
Diffusion Tensor Imaging (DTI), Frontal deep white matter, Centrum Semiovale, Internal Capsule, brain stem white matter, FA values
The constant evolution in MRI techniques and its contrast mechanism has made MRI a powerful tool for the diagnosis of any abnormality related to brain. One of the recent applications of MRI is Diffusion Tensor Imaging (DTI). DTI may be used to plot and distinguish the three-dimensional diffusion of water as a function of spatial location (1),(2). Many developmental, aging, and pathologic conditions of the Central Nervous System (CNS) affect the microstructural architecture of the affected tissues. Diffusion-weighted (DW) MRI techniques, such as DTI and FA, are potent probes for evaluating the impact of disease and aging on microstructure because changes in tissue microstructure and organisation will affect the diffusion of water inside tissues. The most commonly applied quantitative parameters derived from DTI scans are Fractional Anisotropy (FA), which is a measure of the directionality of diffusion, and Apparent Diffusion Coefficient (ADC), which measures the magnitude of the diffusion (3).
As a matter of fact, the applications of DTI are rapidly growing because the technique is highly responsive to changes at the cellular and microstructural levels (4). These parameters can be calculated by voxel-based morphometric and ROI based measurement. although voxel-wise analysis is not much operator dependent and more easily automated than ROI analysis, it requires inter-subject registration and image smoothing (5),(6), which may cause errors in the acquired FA values. In the clinical setting, the ROI-based analysis is more readily applicable.
Despite the increase in the usage of DTI application, comparatively very low normal reference data is available which is measured on 3T MRI scanner. In our knowledge there are only three existed studies (7),(8),(9) in which FA and ADC values are measured at 3T MRI scanners. We have expanded the previous work by increasing the number of anatomical regions and a number of subjects with different age groups, hence the primary aim was to determine the normal FA values in 11 regions of the brain at 3T MRI. The secondary aim was to find out the correlation of FA values with age in healthy adult population.
This cross-sectional study was conducted in the department of Radiodiagnosis, Shree Krishna Hospital and Pramukhswami Medical College, Karamsad, Gujarat, India from April 2020 to August 2022. Institutional Ethical Committee (IEC approval no: IEC/HMPCMCE/117/Faculty/14/77/2020) approval was obtained. Participants were selected following a convenient sampling technique and informed consent was taken from all the participants. Total 52 adult patients were selected and were divided in three age groups: 18-40 years, 41-60 years, and >60 years.
Inclusion and Exclusion criteria: Patients who were referred with clinical indication for MRI scan of brain (without and/or with contrast study} were included in the study as standard care of patient. Patients, who had given informed consent were included in an additional MRI DTI sequence for this research study; which took about 12 minutes of additional time. Patients below the age of 18 years and adults who had needed sedation or anaesthesia for MRI scans were excluded from the study.
Brain MRI was performed on participants using 3T MRI Siemens spectra scanner, a head/neck 16 channel 3T Tim coil. First a 3D T1W Sagittal T1_mprage_sag_p2_iso, T2 weighted sequence, and coronal flair sequences were obtained for anatomical guidance and to ensure that there were no unexpected abnormal findings. Diffusion tensor MRI was performed using a single shot, spin echo, echo planar DT sequence named as Ep2d_diff_mddw_20p2_dti with TR=7500 ms, TE=103 ms, FOV=220 mm, number of averages=5, acquisition time=9 mins, bipolar gradients applied in 12 directions (max b factor=8000 s/mm2). None of the subjects had significant abnormalities observed on conventional MRI sequences reported by certified radiologists.
DTI Image Analysis
Carefully and manually, a freehand ROI on colour coded directional maps was drawn, based on principal anisotropy, in 11 different regions on right and left side of brain. Regions were anterior and posterior side of frontal lobe (Table/Fig 1), centrum semiovale (Table/Fig 2), body of the corpus callosum (Table/Fig 3), genu (Table/Fig 4), splenium (Table/Fig 5), posterior limb of internal capsule (Table/Fig 6), midbrain (Table/Fig 7), pons (Table/Fig 8), medulla oblongata (Table/Fig 9) and foramen magnum (Table/Fig 10). To minimise the influence of taking samples at random sites along the tract, we chose certain natural “crossroads or intermediate stations” that are simple to designate, only to ensure that the slices utilised for analysis were as near to the same level as feasible for all of the participants.
The mean FA and standard deviation for each region of the brain (right and left) were calculated and averaged using descriptive statistics. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software version 20. Pearson correlation was used to find out the correlation of FA values with different age groups.
Total 52 adult patients were selected with 33 males and 19 females. The mean age of the study participants was 52 years. The majority of the data was normally distributed, so a parametric test was used to check the normality of FA values at 3T MRI. (Table/Fig 11) shows the mean FA values ranged from 0.280 on the right side of the medulla oblongata to 0.820 on the left side of the splenium.
Normally FA values are supposed to be less than 1 in normal patients and the same was observed in the present study, although minor regional differences were observed in FA values of a few regions which were moderate and within SD of 1. The the (Table/Fig 12) shows combined averaged FA values of both sides.
Correlation values <0.5 reflects weak correlation, between 0.50 to 0.70 is moderate and >0.70 reflects strong correlation. In the 18-40 age group, strong positive correlations were observed in the midbrain on both sides (right & left) with statistical significance of 0.006 on right side (Table/Fig 13).
The FA does not cast any unique specific tissue quality, it is affected by tissue hydration, myelination, cell-packing density, and fibre diameter, as well as directional coherence, FA is often utilised as a barometer of white matter tissue integrity [10,11]. It is very well known that regional values of FA changes in healthy brain parenchyma (12). In present study the FA values were found to be higher in all three parts of corpus callosum (body 0.627, genu 0.767, splenium 0.809) with least FA value in body of the callosum, similarly according to Brander A et al., (12), the body of the corpus callosum had a lower FA than the genu and splenium, which is likely due to its smaller size, which makes its measurement more susceptible to partial volume influence from neighbouring Cerebrospinal Fluid (CSF) gaps. The FA values observed in present study in the three parts of corpus callosum and posterior limb of internal capsule were slightly different from the findings of Lee CEC et al., (7), Huisman TAGM (8), Husnche S (9) (Table/Fig 14), possible reason could be precision and accuracy of the measurement.
The current study is the rarest one where FA values are measured in so many regions of white matter, and hence it was difficult to locate previous studies in which FA values in additional areas, such as the anterior or posterior part of the frontal lobe, centrum semiovale, midbrain, pons, medulla oblongata and cervico-medullary junction were measured at 3T MRI, however the present results (Table/Fig 14) were aligned with the findings of previous studies which showed that high FA values are typically found in white matter areas with constant fibre orientation and closely packed fibres such as corpus callosum, which is a dense bundle of mediolaterally oriented fibres connecting the cerebral hemispheres (12).
The present study findings were consistent with those of earlier studies which reflect that FA values significantly change as the human ages [7,13]. The existing study showed FA values in the posterior limb of the internal capsule in the 19-35 age group were 0.714±0.04, 0.676±0.081 in the 40-65 age group, in the genu of the corpus callosum were 0.806±0.065 in the 19-35 age group and 0.786±0.076 in the 45-60 age group. In Splenium of Corpus Callosum FA values were 0.775±0.052 in the 19-35 age group and 0.777±0.085 in the 45-65 age group (7), however these investigations were restricted to a small number of brain areas.
Lee CEC et al., (7) and Bisdas S et al., (6) investigated age-related changes in white matter microstructure using diffusion tensor imaging and discovered that FA of inferior frontal white matter decreased with age, their finding points to a regional acceleration of white matter degradation as people get older. In 40-60 age group FA values are highly affected in posterior limb of internal capsule. Reduction in FA values suggested that white matter alterations are not limited to prefrontal white matter and that they occur more frequently in the posterior limb of internal capsule than in specific frontal white matter regions (14), however mild to moderate correlation of few areas of brain was observed in 60 above age group. The present study also came up with the DTI protocol which could be utilised for 3T MRI for brain imaging.
Limited number of participants in each age group would be less to confirm the degradation of FA values with age.
In present study FA values are found to be higher in splenium, genu and body of corpus callosum as compared to the other parts of White Matter that could be due to the composition of multiple and histologically heterogeneous tracts. Moderate correlation of FA values in different age groups are also observed in the study which reflects FA values are found to be significantly affected as the human ages.
Date of Submission: Jul 27, 2022
Date of Peer Review: Sep 05, 2022
Date of Acceptance: Nov 22, 2022
Date of Publishing: Jan 01, 2023
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes
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