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25 PEER REVIEWED EXAMPLES BELOW
"There are currently hundreds of peer reviewed studies on TBI using DTI. "
FINALLY - WE CAN CONFIDENTLY MATCH MILD TBI SYMPTOMS WITH SCIENTIFIC PROOF OF INJURY (PLAIN TALK)
The CDC estimates over 3 million traumatic brain injuries a year and the NIH estimates over 90% of those are categorized as mild.
Historically, traditional MRI or CT is used to prove TBI. Traditional MRI and CT do not look closely enough at the brain's white matter tracts, where mild TBI "hides" on a microscopic level and usually returns a negative report.
The difference between traditional MRI and DTI in the diagnosis and imaging of the brain is the difference between shooting a polaroid of a man's brain and putting it under a nuclear microscope.
Diffusion Tensor Imaging (DTI) records the motion of fluid in the brain as the brain is magnetically pulsed from a variety of angles. The result of what we have proven over the last two years is that we can now confidently match pathology with symptoms and we have both the scientific evidence, which has met Frye & Daubert challenges, and the experts to support the findings. DTI results in a 3D model of the brain at almost a molecular level. In short, we can see everything necessary to determine whether or not an injury has occurred.
The significance of this methodology is significant when one considers that over 2 million people a year have episodic mild traumatic brain injuries and most of them are not given the appropriate treatment because the proof of damage was not possible. This has now changed.
It did not come easily. The imaging is nothing without the correct pre scan, scan and post scan process and protocol. The reason for this is simple: Imaging is finally looking at such a small area, within the white matter tracts, that the margin for error disappears. Therefore, the DTI has to be perfect. For it to be perfect, you have to know what perfect looks like. We now know.
The challenges to DTI after post Frye and Daubert come on three levels:
1. Data Acquisition
2. Data Processing and
We are imaging, i.e, recording the motion of fluid in the brain through an incredibly small area. This is important because "mild TBI" can have symptoms that are often as debilitating as "Severe TBI", only with Severe TBI, you are able to see proof such as "blood on the brain" or a "cracked skull," for example.
Mild TBI, as mentioned, hides typically in white matter tracts and can be as small as a ruptured neuron or a severed nerve fiber while still causing tremendous pain, suffering and complications. DTI has been proven to match the area of damage with the symptoms of the patient/client, making it possible to finally properly treat the millions of people who have been forced to go without treatment for too long.
The amount of data captured is enormous and it requires a rigid, detailed, proven, proprietary pre scan, scan and post scan process be followed to ensure the perfect result.
Due to the potential for challenge in the Data Processing step of DTI, it is sometimes preferred to experts in data processing for DTI. This is important because some past challenges to DTI have challenged the processing of the data. It is imperative to take control of this step as well and not automatically rely on the imaging facility - as their processes are consistently reliable when it comes to traditional MRI, but not necessarily with DTI.
The DTI scan provides you the unprecedented FDA approved ability to see microscopically inside the brain. The acquisition process has to be perfect. The processing step has to be perfect. The reporting step on the back end of the entire process has to know what "Perfect" looks like. Conversely, they must know what imperfect looks like. It is not uncommon to reorder the DTI scan. False Positives are not an issue with DTI. The difference in recent and historic injuries due to the amount of detail is clearly seen. It's also very easy to see the difference between episodic injury and neurocognitive degeneration due to age, drugs, alcohol, etc. We're finally looking close enough to consistently prove or disprove Mild Traumatic Brain Injury in the white matter tracts of the brain with great confidence.
COMPILED DATA BELOW
1. DTI CAN EASILY PASS UNDER FRYE OR DAUBERT
You need to stress to any judge that might hear arguments against its use, that DTI is really just another way of looking at MRI data. No one would argue that MR is junk science and no one will argue that DTI is based upon junk science. It has been described in literature as "an exciting" "new and groundbreaking" methodology that has great promise.
Attacks on DTI used to be couched in terms of a Frye standard, as "not generally accepted in the medical community." This argument, as you can see below has long since been disproven and is obviously misguided. There is no question that DTI is an accepted scientific methodology and technology. It is without question accepted within the scientific community. To argue that it is not generally accepted in the medical community is to debate issues such as reimbursement, coding, Medicare and Medicaid funding. Whether or not it is in widespread use depends on whether it can be billed for. This is not a legitimate scientific argument.
There are currently hundreds of peer reviewed studies on TBI using DTI.
Another defense argument is that although there is an agreed abnormality shown in the white matter, we do not know exactly what the ramifications or symptoms of that abnormality will be. However, that goes to the weight and not the admissibility of DTI. Remind defense counsel that in the realm of MRI and diagnosis of traumatic brain injury, that even with MRI there is no direct correlation between the number and the extent of observed brain lesions and long term clinical outcome. (Scheid R. et al. 2004, Sheid R. et al. 2006).
Do we suggest then that MRI abnormalities have no place in discussions on traumatic brain injury? Of course not. You can also look to the ACR Practice Guidelines (American College of Radiology) Edition 2008 which mentions the accepted extended indications for "tractography."
If the defense tries to keep DTI out, keep the focus on the science and whether it is a legitimate science creating the images in question. The answer to that is always yes. If the defense expert wants to argue about the "meaning" of the abnormality shown on DTI, that is a inquiry that is outside the scope of Frye or Daubert (many of the studies that I have listed in the appendix of this material can be cited in any argument against DTI under Frye and Daubert). In addition, the court ruling in the case of Renzetti v. State Farm, Case # CA CE0702078, in Ft. Lauderdale, Dade County, Florida, wherein the issue of the use of DTI passing Frye was "not even close" according to the Judge. A copy of such ruling is attached hereto as Exhibit 1.
2. DTI IS MORE SENSITIVE TO TRAUMATIC BRAIN INJURY THAN MRI OR CT SCAN AND AS IS ESPECIALLY SENSITIVE TO DIFFUSE AXONAL INJURY (DAI)
Without question DTI can show injury to the white matter of the brain which is not able to be seen on MRI, CAT Scan, PET Scan or SPECT. (4, 14, 17, 20, 24). DTI is useful in cases of high velocity change impact, where initial CT and MRI are normal. If the client or patient continues to have cognitive difficulties and cognitive difficulties are assessed on neuropsychological testing, then DTI can be used to show objective evidence of the continued cognitive decline.
DTI has been shown to be sensitive to and to detect brain injury from diffuse axonal injury with more sensitivity than MRI or CT. (1, 7, 14, 18). When the brain is directly impacted, bruising or tearing on the outer most tissue of the brain by the skull upon movement is generally shown in the grey matter. Tissue lost from bruising or tearing is also generally seen in the grey matter and is easily observable on MRI and CT. However, the tissue destruction and changes from diffuse axonal injury, arising from a high speed velocity change tearing or damaging the axons of the brains white matter is clearly best shown by DTI. Keep in mind the evolution of the notion of diffuse axonal injury. I keep a copy of the 1984 Edition of the most widely used neurology textbook in the United States medical schools - Merritts Neurology. Because many of the IME doctors that we encounter across the nation are older rather than younger, many of them went to medical school during or before this books publication. It is astounding to learn and to show that the term "diffuse axonal injury" is not even mentioned in this textbook. The evolution of this term and its meaning has evolved since 1984. For example, when the term first came about it was thought to exist only in the context of severe brain injury cases involving a lengthy coma. Now, we know that DAI exists in a full spectrum of level of injury from mild traumatic brain injury to severe. DTI has been shown to detect white matter abnormalities (DAI) in cases of mild traumatic brain injury and even in cases of very mild traumatic brain injury (VMTBI) (3, 5, 9, 17).
DAI occurs primarily in the white matter so DTI is an essential tool to be able to visualize and explain DAI injury. Abnormalities and destruction of white matter tracts in the brain following a high speed impact are commonly associated with a slowing of processing speed. This is consistent with the destruction or damage to the connecting fibers between hemispheres in the brain and between areas of grey matter resulting in slowing of processing speed. All of this can and does occur in the absence of a focal abnormality on traditional MRI. Hopefully, you will be able to overlap abnormalities between DTI, MRI, PET or SPECT scanning. However, a lack of overlapping injured areas is not essential nor fatal to your case. This is especially so when you are comparing functional testing (PET/SPECT) with structural testing (MR/DTI/CT).
In a high speed velocity change case involving loss of consciousness, the DAI injuries will generally be seen on brain MRI at the "grey-white junction." This occurs because of the slight difference in density between grey and white brain matter. Thus a slippage or shearing injury occurs at the junction. This can and should be distinguished on traditional MRI with punctate lesions or "white matter hyper-intensities" which are commonly seen during the aging process and tend to be scattered throughout the brain. DTI can be used to show consistency between MRI abnormalities due to DAI and in the white matter tracts that connect those areas at the grey-white junction.
3. WHAT DO THE DTI ABNORMALITIES MEAN?
As with brain abnormalities seen on traditional MRI, there has to be a differential diagnosis on the part of your radiologist. Causes for abnormality on DTI that have to be ruled out could be: an old stroke, a prior TBI, a prior brain surgery, prior infectious process such as encephalopathy or history of MS.
The other possible cause of abnormality on DTI could be a congenital process. It could be that some of the white matter connections in the brain were less robust in an individual than normal. General, if that is the case, the abnormalities would tend to be bilateral and global. If, for example, your client has suffered a blow to the left side of the head and shows decreased white matter tracts in that general area on the left side, that would be more consistent with traumatic origin than a congenital one.
Aging causes a reduction in the robustness of the white matter tracts over time. Also, keep in mind that as the brain ages there is a phenomena knows as the "hemispheric asymmetry reduction in older adults" (HAROLD). (Zhihao, L et al 2009). Therefore, with aging in a natural brain, asymmetry are reduced not increased. Therefore an asymmetry in the white matter of an older patient, if differential diagnosis can rule out other causes, is not less likely to be congenital.
Nor can it be argued that abnormalities on DTI are found only in the acute phase of brain injury. It has been found (Kraus, MF et al 2007), that not only do DTI TBI abnormalities exist on a spectrum including mild TBI, but DTI provides objective evidence of TBI even when the injury was sustained years prior to the evaluation.
4. SOME TIPS ON USING DTI TO PROVE DAMAGES AND DEFENDING AGAINST THE IME RADIOLOGIST
The defense will argue there is a lack of "normative data" showing the neuro-radiologist what a normal brain looks like at different ages in regards to white matter tracts. Thus, experts are less able to point to asymmetries or abnormal findings on DTI to show that damage has actually been sustained. One can answer this by showing the numerous studies in which DTI abnormalities in the context of acute or chronic TBI have been matched with performance on neuropsychological test batteries (4, 5, 21). In a recent trial I had involving DTI, the defense neuro-radiologist stated that there was no normative data for an 81 year-old woman with a MTBI. I then asked him (he was really a MRI expert and not a DTI expert) whether there was any MRI normative data regarding an 81 year-old woman with a mild TBI, he stated that there was not. It goes to the weight of the evidence and can be overcome. Always try to have your expert on DTI do both a region of interest (ROI) analysis as well as a full color tractography map of the brain. This is because in most academic studies (which do not care much about speed or costs) regions of interest or particular tiny areas of the brain are individually viewed to determine their FA values. This can be done with current software, although it is more time consuming than allowing the computer to run a full brain color map, which does the same thing on a macro basis. Defense experts will suggest that tractography is less precise and more prone to error than ROI analysis. Therefore, doing both will defeat this argument. The CD of the DTI data can and will be given to defense counsel. With that the defense neuro-radiologist can rerun both tractography and ROI. They can pick any region and try to replicate the original findings. If they choose not to do that, point it out to the jury. They can not suggest that something is probably inaccurate and then choose not to verify that statement by actually looking. Again, try to have as solid a "differential diagnosis" as possible, ruling out as many other possible causes for the abnormalities as possible, then see what common, overlapping abnormalities you can put together. If the asymmetries on DTI are on the left frontal area can you tie it with a blow to the left front of the head? Are the neuropsychological finding consistent with left frontal abnormality? The pictures of the brain are spectacular and convincing. The argument that the "telephone wires" that allow different parts of the brain to talk to each other are down or injured (which is what DTI shows) is easy to make and easy to understand to a jury, especially when they are looking at beautiful color pictures of the white matter tracts themselves and can see where the disruption has occurred.
CITED PEER REVIEW STUDIES
Diffusion-Weighted MRI in Diffuse Axonal Injury of the Brain (Hergan K et al 2002)
Speaking of diffuse axonal injury, the paper notes "lesions are typically located at the greywhite matter interface or along/within fiber tracts, centrum semiovale, fornix, superior and middle cerebellar peduncles and the brain stem." (Citing Parizel PM et al 1998). CT and MRI, tend to underestimate the exact extent of DAI, which is backed up by studies in which patients have shown progressive, global cerebral atrophy on the follow-up after initial imaging did not show pathology (citing Gale SD et al. 1995). Old lesions noted on this study of 98 patients seen with DWI maps. Most of the lesions were identified subcortically, none seen in the cortical grey matter. While lesions were located at known predilection sites of DAI. They did show asymmetry in the abnormal findings.
Diffuse Axonal Injury in Severe Traumatic Brain Injury Visualized Using High-Resolution DTI (Xu J et al 2007)
This study was to investigate whether DTI offers additional information as to the extent of damage not visualized on standard MRI in patients with severe TBI. Nine chronic male patients, 11 controls were recruited. They revealed significant differences in FA (fractional anisotrophy) and MD (mean diffusion) and offered superior sensitivity compared to conventional MRI in diagnosis of the AI. ROI analysis confirmed these results in the investigated regions. (In major white matter tracts, including corpus callosum, internal and external capsule, superior and inferior longitudinal fascicles in the fornix of the TBI group). Importantly, also, the DTI changes were more prominent on the right side that contained the focal pathology in most of the patients and accurately reflected differences in both hemispheres (therefore, asymmetry, as in PET scanning and SPECT scanning is a sign of abnormality in DTI as well in the context of DIA). They noted "in conclusion, DTI holds great promise as a diagnostic tool to identify and quantify the degree of white matter injury in TBI patients."
Diffusor Tensor Imaging in Acute Mild Traumatic Brain Injury in Adolescence (Wilde E.A. et al. (including Bigler) 2008)
This study published in Neurology, looked at patients with MTBI in 10 adolescents one to six days post injury with a Glasgow Coma Scale of 15, and negative CT. Subjects were also administered symptom inventory. Results showed the MTBI group demonstrated FA and diffusion consistent with trauma, which were correlated with severity of post concussive symptoms, not found in the control group. Noted that DTI may prove more sensitive than conventional imaging methods in detecting subtle but clinically meaningful, changes following MTBI and may be critical in refinding MTBI diagnosis, prognosis and management.
Serial Changes in White Matter Diffusion-Tensor Imaging Metrics in Moderate Traumatic Brain Injury and Correlation with Neuro-Cognitive Function (Kumar R. et al 2009)
This study found in the Journal of Neurotrauma, examined 38 TBI patients, some hemorrhagic, some non hemorrhagic, with no apparent DIA on conventional MRI and a Glasgow Coma scale ranging between 9 and 13. The FA and mean diffusivity (MD) were quantified from different regions of the corpus callosum and the peri-ventricular white matter (PWM) within 5 to 14 days and six months following TBI. Patients in all groups showed decreased FA in the anterior limb of the internal capsule (ALIC) and the posterior limb of the internal capsule (PLIC), while the genu of the CC showed a decrease during the early period following TBI that persisted six months later. Patients without abnormalities on conventional MRI and DTI in the initial phase were observed having abnormalities in a few regions at six months, which indicates possible delays of some defects shown on DTI over time. "The changes in FA and MD in the CC and PWM at six months follow up show significant correlation with some of the neuropsychological tests performed in the three groups. DTI demonstrates axonopathy in the acute stages, as well as secondary stages, at six months post-injury in the CC and PWM in regions of normal appearing white matter on conventional MRI."
Diffusion-Tensor Imaging Implicates Prefrontal Axonal Injury in Executive Function Impairment following Very Mild Traumatic Brain Injury (Lipton M.L. et al 2009)
The study was to determined whether frontal white matter diffusion abnormalities could predict acute executive function impairment after mild traumatic brain injury. They studied 20 patients with mild TBI within two weeks of injury and 20 matched controls. Fractional anisotropy (FA) and mean diffusivity (MD) were compared using whole brain voxel analysis. Spearman correlation was performed. Results: multiple clusters of lower frontal white matter FA including the dorsolateral prefrontal cortex, were presented in patients with several clusters also demonstrating higher MD. Patients performed worse on tests of executive functioning and lower DLPFC - FA was significantly correlated with worse executive function performance in patients. Conclusion: impaired executive function following mild TBI is associated with axonal injury involving the DLPFC.
Multifocal White Matter Ultrastructural Abnormalities in Mild Traumatic Brain Injury with Cognitive Disability: a voxel-wise analysis of diffusion tensor imaging (Lipton M.L. et al. 2008)
The purpose of the study was to identify otherwise occult white matter abnormalities in patients suffering persistent cognitive impairment due to MTBI. Performed DTI MRI on 17 patients with an age spread who have cognitive impairment due to mild TBI occurring six months to three years prior. Ten healthy controls. FA and MD images were compared showing an overall shift toward lower FA in patients compared to controls. Areas of significantly decreased FA were found in subject group in corpus callosum, subcortical white matter, and internal capsules bilaterally. Colocated elevation of mean diffusivity (MD) was found in patients within each region. Multiple foci of low white matter FA and high MD are present in cognitively impaired mild TBI patients, with a distribution that conforms to that of diffuse axonal injury. Evaluation of single patients also reveal foci of low FA suggesting that DTI may ultimately be useful for clinical evaluation of individual patients.
Global White Matter Analysis of Diffusion Tensor Images is Predictive of Injury Severity in Traumatic Brain Injury (Benson R. R. et al. 2007)
Notes that conventional clinical neuro-imaging is relatively insensitive to axonal injury in TBI. Compared white matter only FA between 20 heterogeneous TBI patients recruited from Detroit including Detroit Medical Center, including six mild and 14 healthy controls. In all cases including mild TBI patients FA were globally decreased compared with controls. FA properties also correlated with injury severity index by Glasgow Coma Scale and post traumatic amnesia, with mean FA being the best predictor in duration of PTA. Increase diffusion in the short axis dimension, likely reflecting dysmyelination and swelling of axons, accounted for most of the FA decrease. FA changes appear to be correlated with injury severity suggesting a role in early diagnosis and prognosis of TBI.
White Matter Integrity and Cognition in Chronic Traumatic Brain Injury: a diffusion tensor imaging study (Kraus M.F. et al. 2007)
Twenty mild, 17 moderate to severe TBI and 18 controls underwent DTI and neuro psychological testing. Region of interest analysis included anterior and posterior corona radiata cortico-spinal tracts, cingulum fiber bundles, external capsules, forceps minor and major, genu, body and splenium of the corpus callosum, inferior fronto-occipital fasciculus, superior longitudinal fasciculus and sagittal stratum. Cognitive domain scores were calculated from attention and memory testing. Decreased FA was found in all 13 regions of interests for the moderate to severe TBI group but only in the cortico-spinal tract sagittal stratum and superior longitudinal fasciculus for the mild TBI group. White matter load ( measure of total number of regions with reduced FA), was negatively correlated with all cognitive domains. Analysis of diffusivity values suggested that all severities of TBI can result in a degree of axonal damage, while irreversible myelin damage was only apparent for moderate to severe TBI. Emphasizes that white matter changes exists on a spectrum including mild TBI. An index of white matter neuropathology (white matter load) was related to cognitive function, such that greater white matter pathology predicted greater cognitive deficits. Mechanistically, mild TBI matter changes may be primarily due to axonal damages as opposed to myelin damage. More severe injuries impact both. DTI provides an objective means for determining relationship of cognitive deficits to TBI, even in cases where the injury was sustained years prior to the evaluation.
Extent of Microstructural White Matter Injury in Postconcussive Symdrome Correlates with Impaired Cognitive Reaction Time: a 3t Diffusion Tensor Imaging Study of Mild Traumatic Brain Injury. (Niogi SN et al 2008)
Noted that DTI could be a useful index of microstructional changes implicated in diffuse axonal injury linked to persistent post concussive symptoms, especially in mild traumatic brain injury, for which conventional MR imaging may lack sensitivity. Thirty-four patients with mild TBI and persistent symptoms were assessed with DTI. FA values of 2.5 standard deviations below the regional average, based upon a control of 26 healthy adults, were coded as exhibiting DAI. Results showed that DTI measures revealed several predominant regions of damage including the anterior corona radiata (41% of patients), uncinate fasciculus (29%), genu of the corpus callosum (21%), inferior longitudinal fasciculus (number of damaged white matter structures quantified by DTI was significantly correlated with mean reaction time on simple cognitive tasks. In contradistinction, the number of traumatic microhemorrhages was uncorrelated with reaction time. Microstructural white matter lesions detected by DTI measures may thus contribute additional diagnostic information related to DAI.
Can We Use Diffusion MRI as a Bio-Marker of Neurodegenerative Processes? (Assaf Y, 2008)
Generally did to show DTI can pass Frey. Talks about the limitations of diffusion imaging (1) diffusion imaging relies on fast acquisition which is know to suffer from severe distortions of image. The problem has been dealt with in two ways, first post processing routines to reshape images to non-distorted form. Second is to use alternative acquisition routes which significantly reduce these artifacts. (2) motions/pulsation artifacts - it is extremely sensitive to motion in the subject. Additional source of motion is blood pulsation, which cases small movements in the brain tissue. (3) if two different white matter fiber systems reside within the same voxel ("crossing fiber") the fractional anisototropy will be artificially reduced and will resemble grey matter. (4) fiber deviation because of the above certainty in fiber orientation estimation may be reduced. (5) some solutions include q-ball imaging (QBI) and persistent angular structure (PAS/MRI).
"Hemispheric Asymmetries in Language-Related Pathways: A combined functional MRI and tractography study" (Powell H.W. et al. 2006)
Left hemispheric specialization for language shows up in anatomical differences. Used fMRI and DWI with tractography, studied ten healthy right handed subjects. They noted "more extensive fronto-temporal connectivity on the left than on the right. Both tract volumes and mean fractional anisotropy (FA) were significantly greater on the left than on the right."
White Matter Asymmetry in the Human Brain: A diffusion tensor MRI study (Buchel C et al, 2004).
Notes that language ability and handedness are likely to be associated with asymmetry of the grey matter and connectivity in the white matter. Using DTI asymmetry of the arcuate fascicle was observed with greater FA in the left hemisphere. "In addition, we show differences related to handedness in the white matter underneath the precentral gyrus contra lateral to the dominate hand, the findings were very robust." They tested for greater FA in the right as compared to the left hemisphere for left handed and greater FA in the left as compared to the right as for right handers. In this analysis only one significant difference was observed in the frontal lobe of the white matter of the precentral gyrus.
The following was also contained in the article:
higher A in the white matter underneath the left insular compared to with insular (Cao et al. 2003) increase of white matter density was observed on the left arcuate fascicle only (Paus et al. 1999). Another study showed that language impaired students with dyslexia showed decreased FA in this region (Klingberg, et al. 2000) which and the decrease in FA was tightly correlated with reading performance. Assuming the asymmetry in the arcuate fascicle develops during language acquisition, one can speculate that the reduced FA in the left arcuate fascicle is in dyslexic is a sign of a deficient lateralization. Asymmetry with greater FA values in the right hemisphere was found in the white matter of the inferior parietal lobe. One study (Guye et al, 2003) showed more extensive connectivity in the dominate (left) hemisphere compared to the right hemisphere; however, overall there are a lot of studies that do not show much asymmetry related to handedness. One limited asymmetry was limited only to males. (Amunts et al 2000)
Quantitative Fiber Tracking of Lateral and Interhemispheric White Matter in Normal Aging: Relations to Timed Performance. (Sulivan E.V. et al 2008)
This article found in the Neurobiology of Aging states in its preface that axonal damage has been associated with decreased FA and a disproportionate increase in longitudinal relative to transverse diffusivity (Song et al 2003). The general consensus is that with aging, anisotrophy and FA in white matter declines and it is accompanied by an increase in diffusivity. The age effects are regional diverse and typically show an interior-posterior gradient of anisotrophy decline (Ardekani, et al 2007; Bhagat 2004; Bucur et al 2007 etc, etc). With a few exceptions this aging pattern in similar in men and women.
Recently they observed lower FA, higher diffusivity and fewer image defined fibers in the anterior but not the posterior segments of the corpus callosum in ten elderly compared with ten young healthy men and women. (Sullivan et al 2006)
Table 2, showing ANOVAs for bilateral DTI fiber metrics may be of some help. They also noted "decreases in FA with age were typically modest, with the prominent age effect in the frontal forceps."
Interestingly, they did neuropsychological scores to try to match them up with the findings on DTI. The digit symbol scores results correlated with FA or diffusivity in several lateral fiber bundles including the fornix, internal and external capsules, frontal forceps, superior longitudinal fasciculus and in three of the six callosal sectors. They also tried to figure out if DTI/performance correlation were mediated by age alone and found that "in no case did age make an independent contribution to the relationship with the fine finger movement scores beyond the independent contributions from the DTI measures of fiber integrity, however age was a predominate factor in predicting digit scores."
Cerebral Fractional Anisotrophy Score in Trauma Patients: A new indicator or white matter injury after trauma. (Ptak, T. et al. 2003)
Fifteen patients randomly selected from trauma surgery service, thirty controlled patients randomly selected from the ER, they note the DTI has been used for diagnosing acute stroke for seven years, non- stroke use of this technology has not showed the same specificity, sensitivity or widespread acceptance. "It notes post traumatic diffuse axonal injury has been evaluated using diffusion tensor imaging (cites Hergan K. et al. "Diffusion weighted MRI in diffuse axonal injury of the brain" 2002) the studies with regard "to clinical usefulness are yet to appear." FA has also been applied to evaluation of post traumatic diffuse axonal injury (cites Arfanakis K. et al "Diffusion Tensor MR Imaging in Diffuse Axonal Injury" 2002). They noted "the statistically significant differences in mean FA values between trauma and controlled subjects were noted in all but one white matter region."
Good statement: "diffusion tensor imaging has been shown to give indications of significant head injury even in the face of normal findings on conventional MRI and CT." (Citing Rugg-Gunn et al "Diffusion Imaging Shows Abnormalities After Blunt Head Trauma When Conventional Magnetic Resonance Imaging is Normal." 2001)
Reduced Fractional Anisotropy on DTI Imaging After Hypoxic-Ischemic Encephalopathy. (Ward P et al 2006)
Good for Frey and DTI. Twenty infants with HIE and controlled infants studied. FA was reduced in moderate brain injury after HIE and may reflect breakdown of white matter organization. FA values continue to decrease over time.
Fractional Anisotropy for Assessment of White Matter Tracts Injury in Methylmalonic Acidemia (Gao Y et al 2009)
MMA is an inborn genetic metabolism problem which presents with neurological symptoms relating to white matter injury. Twelve patients with MMA, all of whom had negative MRI findings, were given an MRI with DTI. Results showed statistically significant reduction in DTI FA value of the frontal white matter, temporal white matter and occipital white matter.
Diffusion Tensor Imaging of Acute Mild Traumatic Brain Injury in Adolescents (Wilde EA et al 2008)
DTI tractography of the corpus callosum was performed in ten adolescents with MTBI one to six days post injury with a Glasgow Coma Scale of 15, negative CT. The MTBI group demonstrated decreased FA and decreased diffusion coefficient and radial diffusivity and more intense postconcussion symptoms and emotional distress compared to the controlled group. DTI may prove to be more sensitive than conventional imaging methods in detecting subtle but clinically meaningful, changes following MTBI and may be critical in refining MTBI diagnosis, prognosis and management.
Diffusion Tensor Imaging During Recovery from Severe Traumatic Brain Injury and Relation to Clinical Outcome: a longitudinal study. (Sidaros A et al 2008)
This study in the journal Brain, performed DTI on 30 severely brain injured patients and normals. They did the DTI near the time of injury and did a follow-up between nine and fifteen months post trauma. Interesting, they found that in the patients who had a poorer outcome the abnormal and low rates of FA were unchanged between the initial test and the follow-up testing over a year later. In patients who had a recovery, the FA and DTI were changed back to normal over the time period. All of these patients had abnormalities consistent with DAI on normal MRIs as well. There was correlation with clinical outcome. (Cites Arfanakis et al 2002 as well as Inglese et al study for the proposition that even mild TBI patients have found DTI abnormalities undetected by conventional MRI, clearly indicating that DTI is more sensitive to traumatic white matter injury than conventional imaging).
Cautions that in the centrum semiobale (CSO) there is a limitation on DTI because of the overlapping fibers which could explain the increase of FA over time in this area noted in the study. In contrast, the other areas did not have this problem. Future studies using more advanced techniques including q-ball imaging (Tuch, 2004) may allow for improvement.
Diffusion Tensor Imaging in Mild Cognitive Impairment and Alzheimers Disease: a review. (Chua, C et al 2008)
A limitation to DTI is its inability to demonstrate spatial and directional diffusion as it is limited by a voxel measurement. To overcome these limitations the DTI data must undergo postprocessing. There are three methods of DTI post processing (1) ROI defining a region of interest in the brain. Recognized as gold standard. Drawback is that it is time consuming susceptible to bias. (2) voxal-based analysis, analyzing whole brain using statistically parametric mapping. This method avoids rater bias. Drawback is "the questionable assumption as to whether a specific location in the brain is truly identical in all subjects, especially so in an aged brain whereby structures atrophic and will not match up even after the process of smoothing to rectify the inequalities in the normalization process." (3) TBSS (Tract base spacial statistics) in comparison of the advantages and disadvantages of these three types is on Table 1 page 85.
Post mortem brains in the aging have demonstrated decrease in mylinated fibers in the white matter and white matter hyperintensities. "This suggest that reduction in neural connectivity could be a possible contributor to cognitive decline in normal aging. DTI changes in the frontal white matter showing decreased FA and increased MD with age have been correlated with performance and neuropsychological testing. The three cognitive domains of executive functioning, working memory and processing informational speed support the notion that white matter connectivity is interval in cognitive performance" (Charlton RA et al. 2006 "White Matter Damage on DTI Correlates With Age Related Cognitive Decline")
Anterior cingulum fibers which are part of the frontal circuitry were found to have severe age related decline in anisotropy.All comparative cross sectional DTI studies involving MCI (Mild cognitive impairment) in controlled subjects have showed consistent findings of white matter microstructural changes in parahippocampal white matter, splenium of the corpus callosum, temporal white matter, parietal white matter and posterior cingulum. They have also demonstrated greater posterior than anterior involvement. Only one study found an reduction in anisotrophy in the frontal white matter. In addition the centrum semiovale was found to have significant increase in diffusivity.
Table 3 in this study is very important and lists significant DTI findings in different studies in mild cognitive impairment.
In conclusion it states DTI and MCI is a promising area for research has potential for early recognition tool in detecting subtle white matter changes that appear normal on structural MRI.
Diffusion Imaging Shows Abnormalities After Blunt Head Trauma When Conventional Magnetic Resonance Imaging is Normal (Rugg-Gunn F.J. et al 2009)
Two patients with severe brain injury underwent DTI diffusion (but not tractography) and DWI. Abnormalities, thought to be from diffuse axonal injury, were noted on the DWI that were not observable on MRI. They concluded "abnormalities of diffusion in patients with severe head injury and unremarkable conventional MRI (recommended that diffusion gradients plied in at least six directions must be performed rather than only three, which may result in abnormalities being overlooked) our results suggest diffusion tensor imaging is a useful quantitative imaging method after head injury, and is more sensitive than conventional MRI."
Evidence for White Matter Disruption in Traumatic Brain Injury Without Macroscopic Lesions. Najayama N et al 2006)
Twenty-three patients were studied in the chronic stage after severe TBI velocity change type brain injury post coma. All patients were chosen because they had the lack of discernable lesions in the brain on MRI. Neuropsychological testing was done.
The results showed lower values of FA in the patients with TBI than in controls. Marked decreases in FA values in the corpus callosum, in other regions, no marked increase or decrease was noted. Abnormalities in the corpus callosum and fornix white matter were found, consistent with reports pointing to the vulnerability of these areas of patients with moderate to severe TBI.
Serial Evaluation of Diffusion Tensor Brain Fiber Tracking in a Patient with Severe Diffuse Axonal Injury. (Naganawa S et al 2004)
This study has some excellent images.
Diffusion Tensor Imaging as Potential Biomarker of White Matter Injury in Diffuse Axonal Injury. (Huisman T et al 2003)
It seems to give us a lot of evidence to validate the use of DTI in brain imaging and trauma injury cases in general.
Diffusion Tensor MR Imaging in Diffuse Axonal Injury. (Arfanakis K et al 2002)
Five patients with mild traumatic brain injury were studied. There is also a great explanation of diffuse axonal injury in this article. CT images of all patients showed no abnormalities.On page 798 of the study there is a comparison of hemispheres in patients with mild traumatic brain injury an healthy controlled subjects.
Challenges to DTI
DTI has come under attack by defendant attorneys working with insurance companies. “Diffusion tensor imaging is a useful diagnostic tool in research and it is evident from group analysis that DTI can identify Traumatic Brain Injury-associated changes in the brain across a range of injury severity, from mild to severe DTI. The argument, however, is this finding is based primarily upon group analyses and there is not conclusive evidence to date that DTI can be used for a diagnosis … at the individual patient level. This argument ignores a large quantity of peer-reviewed scientific literature supporting the clinical use of DTI and ignores that DTI is being used at Walter Reed Army Medical Center to detect and treat wounded service members returning from Afghanistan and Iraq.” Bruce H. Stern, DIFFUSION TENSOR IMAGING Objective Proof of Traumatic Brain Injury, New Jersey Lawyer, the Mag. 11, 12.
Florida Courts Uphold the Use of Diffusion Tensor Imaging
A Hillsborough County, Florida trial court denied a defendant’s Frye challenge regarding the admissibility of MRI with DTI. Hammer v. Sentinel Ins. Co., Case No. 08-019984 (13th Judicial Circuit, Hillsborough County, FL, September 27, 2010).
The Hillsborough trial court stated the DTI is “neither new nor novel science and that plaintiff had demonstrated that the basis underlying principles of DTI had been sufficiently tested and accepted by the relevant scientific and medical communities.
Plaintiff presented the expert testimony of David Herbst, M.D., a Board Certified radiologist, who testified that DTI studies are definitely accepted by practicing radiologists and are depended upon by physicians who order them to assist in diagnosing and treating traumatic brain injuries. The court also buttressed its findings with the position of the American College of Radiology, which defined practice guidelines and technical standards for radiologic practice on the performance and interpretation of Magnetic Resonance Imaging of the brain, which clearly provides that indications for MRI of the brain with diffusion imaging, if available, is helpful in many indications, including, but not limited to, acute and chronic neurologic deficits, headache, mental status change suspicious of non-accident trauma and post-traumatic conditions, among others.” 1 Stern and Brown, Litigating Brain Injuries § 6:12.40.