Reliability of the freehand region-of-interest method in quantitative cerebral diffusion tensor imaging.

BACKGROUND: Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique used for evaluating changes in the white matter in brain parenchyma. The reliability of quantitative DTI analysis is influenced by several factors, such as the imaging protocol, pre-processing and post-processing methods, and selected diffusion parameters. The region-of-interest (ROI) method is most widely used of the post-processing methods because it is found in commercial software. The focus of our research was to study the reliability of the freehand ROI method using various intra- and inter-observer analyses. METHODS: This study included 40 neurologically healthy participants who underwent diffusion MRI of the brain with a 3 T scanner. The measurements were performed at nine different anatomical locations using a freehand ROI method. The data extracted from the ROIs included the regional mean values, intra- and inter-observer variability and reliability. The used DTI parameters were fractional anisotropy (FA), the apparent diffusion coefficient (ADC), and axial (AD) and radial (RD) diffusivity. RESULTS: The average intra-class correlation coefficient (ICC) of the intra-observer was found to be 0.9 (excellent). The single ICC results were excellent (> 0.8) or adequate (> 0.69) in eight out of the nine regions in terms of FA and ADC. The most reliable results were found in the frontobasal regions. Significant differences between age groups were also found in the frontobasal regions. Specifically, the FA and AD values were significantly higher and the RD values lower in the youngest age group (18-30 years) compared to the other age groups. CONCLUSIONS: The quantitative freehand ROI method can be considered highly reliable for the average ICC and mostly adequate for the single ICC. The freehand method is suitable for research work with a well-experienced observer. Measurements should be performed at least twice in the same region to ensure that the results are sufficiently reliable. In our study, reliability was slightly undermined by artifacts in some regions such as the cerebral peduncle and centrum semiovale. From a clinical point of view, the results are most reliable in adults under the age of 30, when age-related changes in brain white matter have not yet occurred.

Acute mild traumatic brain injury is not associated with white matter change on diffusion tensor imaging.

This study was designed to (i) evaluate the influence of age on diffusion tensor imaging measures of white matter assessed using tract-based spatial statistics; (ii) determine if mild traumatic brain injury is associated with microstructural changes in white matter, in the acute phase following injury, in a large homogenous sample that was carefully screened for pre-injury medical, psychiatric, or neurological problems; and (iii) examine if injury severity is related to white matter changes. Participants were 75 patients with acute mild traumatic brain injury (age = 37.2 ± 12.0 years, 45 males and 30 females) and 40 controls (age = 40.6 ± 12.2 yrs, 20 males and 20 females). Age effects were analysed by comparing control subgroups aged 31-40, 41-50, and 51-60 years against a group of 18-30-year-old control subjects. Widespread statistically significant areas of abnormal diffusion tensor measures were observed in older groups. Patients and controls were compared using age and gender as covariates and in age- and gender-matched subgroups. Subgroups of patients with more severe injuries were compared to age-and gender-matched controls. No significant differences were detected in patient-control or severity analyses (all P-value > 0.01). In this large, carefully screened sample, acute mild traumatic brain injury was not associated with diffusion tensor imaging abnormalities detectable with tract-based spatial statistics.

Hemispheric asymmetry measured by texture analysis and diffusion tensor imaging in two multiple sclerosis subtypes.

BACKGROUND: This paper addresses two subtypes of multiple sclerosis (MS), primary progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS). The separation of PPMS and RRMS is challenging in certain cases. PURPOSE: To quantitatively determine MS subtypes using texture analysis (TA) and diffusion tensor imaging (DTI). MATERIAL AND METHODS: T1-weighted (T1W) magnetic resonance imaging (MRI) and DTI of the left and right brain hemispheres of 17 patients with PPMS and 19 patients with RRMS were studied. Areas of the caudate nucleus and thalamus were investigated as normal appearing gray matter (NAGM), and areas of the cerebral peduncle and centrum semiovale were investigated as normal appearing white matter (NAWM). The described locations were symmetrical and were accurately marked. TA was performed on the T1W images, and the fractional anisotropy and apparent diffusion coefficient were determined from the DTI data. RESULTS: Hemispherical differences were found with both TA and DTI. Several texture and diffusion tensor parameter values calculated for the left and right hemispheres of the patients showed statistically significant differences. The patients with RRMS had greater significant differences (P < 0.01) in the thalamus between the hemispheres than did the patients with PPMS. The TA classification accuracy of the PPMS and RRMS subtypes was above 80%. CONCLUSION: TA can be helpful when distinguishing between PPMS and RRMS, while DTI appears to reveal the hemispherical asymmetry of RRMS patients.

Diffusion tensor imaging of the cervical spinal cord in healthy adult population: normative values and measurement reproducibility at 3T MRI.

BACKGROUND: Compared to diffusion tensor imaging (DTI) of the brain, there is a paucity of reports addressing the applicability of DTI in the evaluation of the spinal cord. Most normative data of cervical spinal cord DTI consist of relatively small and arbitrarily collected populations. Comprehensive normative data are necessary for clinical decision-making. PURPOSE: To establish normal values for cervical spinal cord DTI metrics with region of interest (ROI)- and fiber tractography (FT)-based measurements and to assess the reproducibility of both measurement methods. MATERIAL AND METHODS: Forty healthy adults underwent cervical spinal cord 3T MRI. Sagittal and axial conventional T2 sequences and DTI in the axial plane were performed. Whole cord fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were determined at different cervical levels from C2 to C7 using the ROI method. DTI metrics (FA, axial, and radial diffusivities based on eigenvalues λ1, λ2, and λ3, and ADC) of the lateral and posterior funicles were measured at C3 level. FA and ADC of the whole cord and the lateral and posterior funicles were also measured using quantitative tractography. Intra- and inter-observer variation of the measurement methods were assessed. RESULTS: Whole cord FA values decreased and ADC values increased in the rostral to caudal direction from C2 to C7. Between the individual white matter funicles no statistically significant difference for FA or ADC values was found. Both axial diffusivity and radial diffusivity of both lateral funicles differed significantly from those of the posterior funicle. Neither gender nor age correlated with any of the DTI metrics. Intra-observer variation of the measurements for whole cord FA and ADC showed almost perfect agreement with both ROI and tractography-based measurements. There was more variation in measurements of individual columns. Inter-observer agreement varied from moderate to strong for whole cord FA and ADC. CONCLUSION: Both ROI- and FT-based measurements are applicable methods yielding reproducible results for cervical spinal cord DTI metrics. Normative values for both measurement methods are presented.

Technical Performance Assessment and Quality Control of Ultrasound Device Monitors.

The purpose of this study was to investigate and evaluate the current technical performance of ultrasound imaging device displays. Altogether 53 ultrasound device displays were evaluated in two hospital districts of Finland. The performance of the displays was evaluated with tests and test patterns developed by American Association of Physicists in Medicine (AAPM). Minimum, maximum and ambient luminances (Lmin,Lmax,Lamb) were measured. Ambient ratio (AR), luminance ratio (LR), [Formula: see text] and [Formula: see text] were calculated, and luminance uniformity, defined as deviation from the median (MLD), was evaluated. The results indicate that none of the measured displays fulfill the AAPM Task Group (TG) 270 maximum luminance recommendation for diagnostic displays. A majority (32/53, 60%) of the displays fail the AAPM TG270 acceptable level for secondary displays as well. Only 3 of 53 (6%) displays were at the acceptable level for diagnostic displays. Also, for most of the displays (41/53, 77%), [Formula: see text] was under the diagnostic acceptable level. Ambient ratios exceeded the acceptable limit in 31 of 53 (58%) displays. Luminance ratios, on the other hand, were within acceptable levels for the majority of displays (38/53, 72%). All devices passed the AAPM requirement for luminance uniformity (MLD). The results indicate that the maximum luminance and minimum luminance of most displays are not sufficient. AAPM, the Society for Imaging Informatics in Medicine and the American College of Radiology introduced the updated luminance [Formula: see text] and [Formula: see text] criteria in 2012. All ultrasound displays should at least fulfill the AAPM TG18 secondary display minimum criteria. Even so, 6 of 53 (11%) fail. The newest displays should be expected to fulfill the revised AAPM TG270 criteria as well. Display technology has developed, and therefore, monitor testing needs to be updated.

Repeatability and variation of region-of-interest methods using quantitative diffusion tensor MR imaging of the brain.

BACKGROUND: Diffusion tensor imaging (DTI) is increasingly used in various diseases as a clinical tool for assessing the integrity of the brain's white matter. Reduced fractional anisotropy (FA) and an increased apparent diffusion coefficient (ADC) are nonspecific findings in most pathological processes affecting the brain's parenchyma. At present, there is no gold standard for validating diffusion measures, which are dependent on the scanning protocols, methods of the softwares and observers. Therefore, the normal variation and repeatability effects on commonly-derived measures should be carefully examined. METHODS: Thirty healthy volunteers (mean age 37.8 years, SD 11.4) underwent DTI of the brain with 3T MRI. Region-of-interest (ROI) -based measurements were calculated at eleven anatomical locations in the pyramidal tracts, corpus callosum and frontobasal area. Two ROI-based methods, the circular method (CM) and the freehand method (FM), were compared. Both methods were also compared by performing measurements on a DTI phantom. The intra- and inter-observer variability (coefficient of variation, or CV%) and repeatability (intra-class correlation coefficient, or ICC) were assessed for FA and ADC values obtained using both ROI methods. RESULTS: The mean FA values for all of the regions were 0.663 with the CM and 0.621 with the FM. For both methods, the FA was highest in the splenium of the corpus callosum. The mean ADC value was 0.727 ×10-3 mm2/s with the CM and 0.747 ×10-3 mm2/s with the FM, and both methods found the ADC to be lowest in the corona radiata. The CV percentages of the derived measures were < 13% with the CM and < 10% with the FM. In most of the regions, the ICCs were excellent or moderate for both methods. With the CM, the highest ICC for FA was in the posterior limb of the internal capsule (0.90), and with the FM, it was in the corona radiata (0.86). For ADC, the highest ICC was found in the genu of the corpus callosum (0.93) with the CM and in the uncinate fasciculus (0.92) with FM. CONCLUSIONS: With both ROI-based methods variability was low and repeatability was moderate. The circular method gave higher repeatability, but variation was slightly lower using the freehand method. The circular method can be recommended for the posterior limb of the internal capsule and splenium of the corpus callosum, and the freehand method for the corona radiata.

To exclude or not to exclude: white matter hyperintensities in diffusion tensor imaging research.

OBJECTIVE: A practical methodological issue for diffusion tensor imaging (DTI) researchers is determining what to do about incidental findings, such as white matter hyperintensities (WMHI). The purpose of this study was to compare healthy control subjects with or without WMHIs on whole brain DTI. METHOD: Participants were 30 subjects (age = 37.7, SD = 11.3, Range = 18-60; 70% female) who had no known developmental, general medical, neurological or psychiatric condition that could have had an adverse affect on brain morphology. RESULTS: MRI (3 Tesla) revealed, at minimum, a WMHI in eight subjects (26.7%). Fractional anisotropy (FA) was calculated for 19 regions of interest (ROI). Frequency distributions of FA scores for the 19 ROIs were calculated. The 10th percentile for each ROI was selected as a cut-off score. Having four or more low FA scores occurred in 16.7%. More subjects with incidental findings met criterion for low FA scores (37.5%), compared to 9.1% of subjects with no findings. When subjects with minor WMHIs were retained and only those with multiple incidental findings were excluded, 8.3% of the retained subjects met criterion for low FA scores compared to 50.0% of the excluded subjects. CONCLUSIONS: The decision to include or exclude subjects who have incidental findings can influence the results of a study.

Ability of ultrasound imaging to detect erosions in a bone phantom model.

OBJECTIVES: The authors examined the validity, interobserver reliability and interscanner variation in detecting bone erosions with ultrasonography using a custom-made phantom. METHODS: 21 bovine bones were used. Artificial erosions were made into 15 bones and six bones were left as controls. In the processed bones the numbers of erosions, their depths and widths varied between 1-7, 1-4 and 1.5-5 mm, respectively. Each bone was coated with polyvinyl alcohol cryogel to mimic overlying soft tissue and to hide the erosions. Four musculoskeletal sonography experts scanned the 21 blind-coded phantoms using one of the three sets of ultrasound equipment. Finally, quality assurance measurements of the ultrasound equipment was carried out using two additional bone samples. RESULTS: The sonographers detected the erosions successfully with ultrasound. The mean correlation coefficient for a correct result in terms of the number of erosions detected was 0.88 (range 0.75-0.975). The overall Cohen's kappa coefficient for interobserver agreement was 0.683 in terms of discrimination between healthy bones and bones with erosions. The different sets of equipment showed that their overall performance was equal. CONCLUSIONS: The sonographers had good correlations with the number of erosions and they were successful in separating healthy bones from bones with erosions. It seems that neither depth nor width is crucial but that in experimental conditions a 1.5 mm erosion width was the limit for the resolution with current ultrasound equipment. Ultrasound is a valid and reliable method of detecting cortical bone erosions in vitro, when the round erosion is at least 1 mm deep and 1.5 mm wide.

Diffusion tensor imaging and disability progression in multiple sclerosis: A 4-year follow-up study.

OBJECTIVES: Diffusion tensor imaging (DTI) is sensitive technique to detect widespread changes in water diffusivity in the normal-appearing white matter (NAWM) that appears unaffected in conventional magnetic resonance imaging. We aimed to investigate the prognostic value and stability of DTI indices in the NAWM of the brain in an assessment of disability progression in patients with a relapsing-onset multiple sclerosis (MS). METHODS: Forty-six MS patients were studied for DTI indices (fractional anisotropy (FA), mean diffusivity (MD), radial (RD), and axial (AD) diffusivity) in the NAWM of the corpus callosum (CC) and the internal capsule at baseline and at 1 year after. DTI analysis for 10 healthy controls was also performed at baseline. Simultaneously, focal brain lesion volume and atrophy measurements were done at baseline for MS patients. Associations between DTI indices, volumetric measurements, and disability progression over 4 years were studied by multivariate logistic regression analysis. RESULTS: At baseline, most DTI metrics differed significantly between MS patients and healthy controls. There was tendency for associations between baseline DTI indices in the CC and disability progression (p < 0.05). Changes in DTI indices over 1 year were observed only in the CC (p < 0.008), and those changes were not found to predict clinical worsening over 4 years. Clear-cut association with disability progression was not detected for baseline volumetric measurements. CONCLUSION: Aberrant diffusivity measures in the NAWM of the CC may provide additional information for individual disability progression over 4 years in MS with the relapsing-onset disease. CC may be a good target for DTI measurements in monitoring disease activity in MS, and more studies are needed to assess the related prognostic potential.

Possible confounding factors on cerebral diffusion tensor imaging measurements.

BACKGROUND: Diffusion tensor imaging (DTI) is prone to numerous systemic confounding factors that should be acknowledged to avoid false conclusions. PURPOSE: To investigate the possible effects of age, gender, smoking, alcohol consumption, and education on cerebral DTI parameters in a generally healthy homogenous sample with no neurological or psychiatric diseases. MATERIAL AND METHODS: Forty (n = 40) subjects (mean age, 40.3 years; SD, 12.3) underwent brain DTI with 3 T magnetic resonance imaging (MRI). At enrolment, all the subjects were interviewed with respect to general health, education, history of smoking, and alcohol consumption. Studied DTI parameters included: (i) fractional anisotropy (FA); and (ii) apparent diffusion coefficient (ADC). Region-of-interest (ROI)-based measurements were estimated at 13 anatomical locations bilaterally on the axial images, except for the corpus callosum in which the ROIs were placed on the sagittal images. Circular ROI measurements were mainly used. Freehand ROI method was used with the forceps minor, uncinate fasciculus, and thalamus. Intra-observer variability and repeatability were assessed. RESULTS: The most consistent finding was that aging decreased FA values in the frontal brain regions. Regarding the other confounding factors, the results were discontinuous and no concrete conclusions could be drawn from these findings. In general, intra-observer repeatability of the DTI measurement was considered relatively good. CONCLUSION: Age should be noted as considerable confounding factors in ROI-based DTI analysis. More research on the effects of gender, smoking, alcohol consumption, and education is needed.

A prospective biopsychosocial study of the persistent post-concussion symptoms following mild traumatic brain injury.

This study examined multiple biopsychosocial factors relating to post-concussion symptom (PCS) reporting in patients with mild traumatic brain injuries (mTBI), including structural (computed tomography and magnetic resonance imaging [MRI]) and microstructural neuroimaging (diffusion tensor imaging [DTI]). Patients with mTBIs completed several questionnaires and cognitive testing at approximately one month (n=126) and one year (n=103) post-injury. At approximately three weeks post-injury, DTI was undertaken using a Siemens 3T scanner in a subgroup (n=71). Measures of fractional anisotropy were calculated for 16 regions of interest (ROIs) and measures of apparent diffusion coefficient were calculated for 10 ROIs. Patients were compared with healthy control subjects. Using International Classification of Diseases, Tenth Revision (ICD-10) PCS criteria and mild or greater symptom reporting, 59% of the mTBI sample met criteria at one month and 38% met criteria at one year. However, 31% of the healthy control sample also met criteria for the syndrome-illustrating a high false-positive rate. Significant predictors of ICD-10 PCS at one month were pre-injury mental health problems and the presence of extra-cranial bodily injuries. Being symptomatic at one month was a significant predictor of being symptomatic at one year, and depression was significantly related to PCS at both one month and one year. Intracranial abnormalities visible on MRI were present in 12.1% of this sample, and multifocal areas of unusual white matter as measured by DTI were present in 50.7% (compared with 12.4% of controls). Structural MRI abnormalities and microstructural white matter findings were not significantly associated with greater post-concussion symptom reporting. The personal experience and reporting of post-concussion symptoms is likely individualized, representing the cumulative effect of multiple variables, such as genetics, mental health history, current life stress, medical problems, chronic pain, depression, personality factors, and other psychosocial and environmental factors. The extent to which damage to the structure of the brain contributes to the persistence of post-concussion symptoms remains unclear.

Longitudinal assessment of clinically isolated syndrome with diffusion tensor imaging and volumetric MRI.

The potential of diffusion tensor imaging (DTI) indices and volumes of focal lesions on conventional magnetic resonance imaging to predict conversion to multiple sclerosis (MS) was analyzed in subjects with clinically isolated syndrome (CIS) over 4 years. Twenty patients with CIS and 10 healthy controls were included in the study. The data showed an association between the volumes of T1 and fluid-attenuated inversion recovery (FLAIR) lesions and conversion to MS (T1: P=.02; FLAIR: P=.02). The worsening of DTI indices (mean diffusivity and fractional anisotropy) was primarily seen in patients progressing to MS, but clear-cut association with conversion could not be detected.

Biopsychosocial outcome after uncomplicated mild traumatic brain injury.

The purpose of this study was to examine the biopsychosocial outcome from uncomplicated mild traumatic brain injury (MTBI) within the first 3 weeks post injury. Participants were 48 prospectively enrolled patients from the Emergency Department of Tampere University Hospital, Finland, who sustained an uncomplicated MTBI. At 3 weeks post injury, diffusion tensor imaging (DTI) of the whole brain was undertaken using a Siemens 3T scanner. Measures of fractional anisotropy (FA) were calculated for 16 regions of interest (ROIs) and measures of apparent diffusion coefficient (ADC) were calculated for 10 ROIs. Twenty-four healthy control participants also completed DTI of the whole brain for comparison. Participants were administered a brief battery of self-report (e.g., postconcussion symptoms, depression, and fatigue) and neurocognitive measures (e.g., verbal learning and memory). There were no significant differences between the uncomplicated MTBI and healthy control group on any measures of learning and memory. Compared to the control group, the uncomplicated MTBI group reported a greater number of postconcussion symptoms and fatigue, but not depression. When considering all DTI ROIs simultaneously, the MTBI group had a significantly larger number of low DTI measures (FA values) compared to the healthy controls. MTBI patients with multifocal white matter changes did not show evidence of worse symptoms, cognitive impairment, or slower return to work compared to MTBI patients with broadly normal white matter.

Assessing the state of chronic spinal cord injury using diffusion tensor imaging.

The aim of this study was to quantify the association between diffusion tensor imaging (DTI) parameters of the cervical spinal cord and neurological disability in patients with chronic traumatic spinal cord injury (SCI). A cervical spinal cord 3T magnetic resonance imaging (MRI) with DTI sequences was performed on 28 patients with chronic traumatic SCI and 40 healthy control subjects. DTI metrics, including fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD), were calculated within the normal-appearing spinal cord area at levels C2 or C3. Clinical assessment of the patients was performed according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and the motor subscale of the Functional Independence Measure (FIM). The FA values of the patients with SCI were significantly lower than those of healthy control subjects (p<0.000001). In contrast, the ADC and RD values of these patients were significantly higher than those of control subjects (ADC p<0.0001, RD p<0.00001). In patients with SCI, the FA values were positively correlated with the motor (pr=0.56, p<0.01) and sensory (pr=0.66, p<0.001) scores of ISNCSCI and with the motor subscale of FIM (pr=0.51, p<0.01). DTI revealed spinal cord pathology, which was undetectable using conventional MRI. DTI changes in regions that were remote from the site of primary injury were most likely the result of secondary degeneration of white matter tracts. Decreased FA values were correlated with poorer motor and sensory function, as well as a lack of independence in daily living. DTI is a promising quantitative and objective tool that may be used in the clinical assessment of patients with SCI.

Diffusion Tensor Imaging in NAWM and NADGM in MS and CIS: Association with Candidate Biomarkers in Sera.

The aim of this study was to evaluate diffusion tensor imaging (DTI) indices in the corpus callosum and pyramidal tract in normal-appearing white matter (NAWM) and the caudate nucleus and thalamus in deep grey matter (NADGM) in all MS subtypes and clinically isolated syndrome (CIS). Furthermore, it was determined whether these metrics are associated with clinical measures and the serum levels of candidate immune biomarkers. Apparent diffusion coefficients (ADC) values were significantly higher than in controls in all six studied NAWM regions in SPMS, 4/6 regions in RRMS and PPMS and 2/6 regions in CIS. In contrast, decreased fractional anisotropy (FA) values in comparison to controls were detected in 2/6 NAWM regions in SPMS and 1/6 in RRMS and PPMS. In RRMS, the level of neurological disability correlated with thalamic FA values (r = 0.479, P = 0.004). In chronic progressive subtypes and CIS, ADC values of NAWM and NADGM were associated with the levels of MIF, sFas, and sTNF- α . Our data indicate that DTI may be useful in detecting pathological changes in NAWM and NADGM in MS patients and that these changes are related to neurological disability.