use of mri in the diagnosis of a specified pathological condition of the brain

Use of MRI in the diagnosis of a specified pathological condition of the brain



Abstract

The study was conducted in order to examine the volume of selective brain regions

within the less impaired patients suffering from AD. For in-depth analysis, five regions were

chosen. All of these shows that a considerable number of AD patients undergo change due to this

disease, which is evident in the study. The amygdala and the basal forebrain were not

differentiated in AD patients and controls. It was evident that a linear blend of the hippocampus

volumes including the temporal horn was found to be 100% different in patients.

Background

AD stands as a very common cause of dementia which onsets with age and it alone

accounts for more the seventy percent cognitive damages. For those who are nearly 85 years of

age, it is becoming a commonplace disease. Coming fifty years will boost the number of

dementia patients to up to three times they are today. AD refers to the progressive accumulation,

in the human brain, of proteins which are abnormal and thus harmful. This accumulation is the

cause of synaptic, axonal and neuronal impairment. Unfortunately neurobiological changes begin

much earlier than the appearance of the symptoms which is quickly followed by neocortical

impairment.

MRI has become the preferred procedure for diagnosing a large number of potential

problems in many different parts of human body. MRI gives images through a computer

workstation which enhances the images and shows the difference between the healthy tissues and


the unhealthy one. Today MRI is most preferred technique to examine brain parts, the spinal

cord, body joints, abdomen, breast and chest, blood vessels and other parts.

MRI is the abbreviation for magnetic resonance imaging. It is a means to view the images

of the body from inside in order to diagnose various ailments. MRI is more powerful than other

scanning technologies like CAT or X-Rays. MRI’s magnetic field is used with radiofrequency

energy and with the use of a special computer; the health professionals can have a very clear

image of the inside of the body and its structures. Today large numbers of body’s problems are

diagnosed with the use of MRI which is the most preferred process. MRI's of brain, spine joints,

abdomen, breast, vessels, heart and pelvic regions are common practice now.

Prerequisites of patients for MRI analysis

Research into the development of expertise suggests that it takes about ten years to

become expert in any field (Ericssonetal, 1993) and so is MRI. However, the new researcher has

to start somewhere. Here, outlined are the basic areas of knowledge that we think are essential to

becoming an expert at MRI analysis, roughly in order of importance. MRI

Earlier MRI procedures which were done without any incident of safety is no guarantee

that the second MRI examination will also be safe. A simple change in the orientation of the

patient or of the MRI's field strength can completely make a significant change in the scenario.


MRI has been subjected to many pros and cons, including some incidental research on

brain MRI, the Stanford University has updated MRI's non-clinicals benefit clause which relates

to follow-up treatment, which is the sole realm of the patient and the physician. There are certain

guidelines for MRI procedures:

1. MRI should be avoided with the body coil.

2. Magnetic fields should not cross more than 2.0.T

3. Per human subject, the whole body averaged SAR should not be greater than 1.3W/kg

vis-a-vis a subject weighing 70 kg.

4. 10 mT/sec or less should be the time-varying field

5. MIR produces Static magnetic or RF magnetic fields which can adversely affect Pulse

generator setting.

Similarly patients with any metallic foreign body, like pacemaker, Insulin pump,

Pregnancy, Claustrophobia, Kidney problems or Neurostimulators should first be checked by the

radiology staff, who only can determine whether to have MRI or not. Although MRI scan is a

safe and painless process which provides images of organs inside the human body, yet many

patients are very afraid just by the name MRI, so such patients should first be given proper

counseling.

Some studies indicate that T2-signal changes in the basal ganglia and brainstem on 1.5 T

MRI, along with posterior putaminal hypointensity, hyperintense lateral putaminal rim, the ‘hot

cross bun’ sign, and middle cerebellar peduncle hyperintensities and these studies would be


helpful in the diagnosis of this condition. As far as power estimates for trials along with drug

registration are related, these still depend upon the traditional clinical cognitive. But as is well

known, that much efforts have to be made to further such studies and research in this context.

MRI scanners are also undergoing technological evolution and today more sophisticated versions

are being tested to help in the diagnosis more effectively and economically.

Today ASL-MRI has better sensitivity as compared to PET to ascertain changes in the

human brain and thus gives the pathologists a better understanding for the diagnosis of AD. It

also is economical in cost and time and with this ASL-MRI quicker and specific screening of AD

patients is possible.

Introduction

Comparisons have been done, in mildly to severely ailing patients, for regional brain

measure through MRIs, to differentiate brain structure between Alzheimer's disease (AD) and

controls.

Five regions of brain were measure by Seab et al, by the use of light pen, in 7 controls

and 10 AD patients out of whom 4 were mildly impaired. It included hippocampus, ventricular

abd subarachnoid spaces as well as lenticular nucleus and it was revealed that only the

hippocampal measure has overlap between control and patients. Kesslak et al measured the

hippocampus, the parahippocampal gyrus and the striatum in 7 controls and 8 mildly impaired

AD patients and he came to know that a considerable variation is present in the hippocampal and

parahippocampal measures without having any overlap among groups but the group was not


differentiated by volumetric measure of striatum, within the patients of AD and controls it was

not possible to find a difference in the volume of the mammillary organs.

With computerized tomography or CT scan and MRI, these results seem to be consistent

so are they with neuropathological studies that show the medial temporal lobes are very much

affected in AD.

For the sake of examining the volume of a chosen brain region in mildly affected AD

patients, the following study was done. Regions, in total five, which showed considerable

difference in the number of AD patients, were selected for analysis.

Methods

For study, ten subjects were included, eight (4 female, 2 male) who were suffering from

dementia of the Alzheimer type 3 female, 1 male as normal control subjects. Their age bracket

was from 60 to 78 years. Patients with AD had a mean age of 72 years and the mean for the

controls was 65 years, there was not much difference in age as seen in the context of group.

NINCDS/ADRDA criteria were followed for diagnosing the probable AD. Patients with

medical history of etiology were excluded by means of various tests like CT. VDRL etc.

Similarly those having medical history of severe headache, psychiatric problems, epilepsy, or

cancer etc were also not taken. The AD patients were having a score of four on ischemic scale to

check multi-infarct dementia. Their medical history revealed their problems in occupational

works and also memory lapses or impairments. Mini Mental State Examination or MMSE is the


internationally known general test which is carried out to know cognitive functions in the

dementia patients. According to MMSE a score which ranges between 20 and 30 means that

there is only mild impairment of the brain. In this study it was found that 5 out of the 6 patients

suffering from AD have a reading of 20 or greater and have a mean of 22.

This study which was about normal aging, the subjects were normal controls, i.e. the

participants have no history of any malaises like alcoholic habits, psychiatric illness, epilepsy or

caner.

Normal control subjects were also subjected to various laboratory tests to rule out serious

systemic illness and underwent the neuropsychological testing to eliminate the potential of

including persons with cognitive symptoms of a dementing illness.

Clinical Indications and Equipment used

Studies of MRI were done with bird-cage coil on a 1.5-T unit (Magnetom Symphony

Maestro, Siemens Medical Solutions). The imaging protocol included sagittal T1-weighted

images (TR/TE, 426/11; field of view, 230 × 230 mm; matrix size, 128 × 128; slice thickness, 5

mm), axial FLAIR images (9,500/100; field of view, 220 × 220 mm; interpolated matrix size,

256 × 162; slice thickness, 5 mm), and oblique coronal T2-weighted images (4,290/120; field of

view, 220 × 220 mm; matrix size, 320 × 216; slice thickness, 3 mm).


Approximately 120 coronal images were obtained of the occipital poles to the frontal

poles. Every scan was seen from the slice displaying the junction of the calcarine and parieto-

occipital sulci to a slice rostral to the temporal poles. Separate measures were taken for the

structures in both the left and right hemispheres. In total, five regions of the brain were

highlighted and with the help of a computer; volumes of the regions were calculated.

The regions of the brain were segmented depending on the nature of segmentation issues

of each structure. The milestones used to delineate the regions of importance are Amygdala,

Caudally and they are visually portrayed in the legend of figures.

Although CT is faster and is preferred in traumatic patients or acute neuro-emergencies,

but in this case, MRI was a preferred choice as it does not required ionizing radiation and also

because due to physical capabilities being weak, MRI did not call for movements of the patients.

But most of all because MRI has the capacity to reveal greater details, is very sensitie and is the

perfect choice for any diagnosis to find abnormalities with the human brain.

Basal Forebrain: Measurements were availed through three levels of the basal forebrain

and was attained through locating the coronal slice containing anterior commissure. After

demarcating the basal foundation, the interhemispheric surface belonging to the ventricle was

then tracked to the inferior surface belonging to anterior commissure, thereby drawing a semi-

circle following it back to the conjunction of amygdala.


Hippocampus: Outlining it started as soon as the whitish substance of alveus turned

dissemble. Outlines of the hippocampus were labeled, both laterally and superiorly, by inferior

horn of lateral ventricle, medially and inferiorly by the whitish matter that conjoined

parahippocampal gyrus.

Temporal Lobe: Measurement of the temporal lobe started as it appeared first at temporal

pole and included outlining the cortical surface onto the sulci. The outlining of the temporal lobe

stopped when the temporal horn of the lateral ventricle formed the collateral trigone.

Critique

AD research with individuals or groups is quite difficult. There is still lack of theoretical

frameworks that could possibly guide studies, the design and measurement problems, samples of

patients with no systematic diagnosis, affect researchers' lack of knowledge about patients with

AD.

Through this study, it is revealed that AD patients who are not severely impaired, posse

significant changes to hippocampal and temporal horn size. It was also revealed that if these two,

if combined linearly, considerably differentiated 99.9% of patients and controls. Patients and

controls also have a difference in the measure of temporal lobe. Findings are consistent in

affirming that temporal lobes of patients with mild symptoms have significant pathology.

During the disease period, temporal lobe is involved in the early days of the disease

which proves that the hypothesis which says that damage to hippocampal formation is cause of


severe memory problems in AD. It may be noted that various studies have proved the fact that

tests pertaining to delayed recall are successful in differentiating less impaired AD patients from

the normals and other patient groups.

The basal forebrain or the amygdala considerably helped differentiate the lesser impaired

AD patients from the control. The outcome is coherent with neuropathological data showing that

cells in the brain in the patients of AD are being lost and proves that damages are have less

chances to appear in early stages of this disease.

Amygdala when measured suggested that impairment was not detectable by MRI. Yet

Amygdala damage is not consistent throughout. Nearly 40% loss in volume is shown by cortical

nucleus, while the medial basal nucleus shows a loss of nearly 15%. Basal forebrain

measurements showed any considerable trend, suggesting damage to the basal forebrain might

not have been present with the onset of AD in patients. It proves that therapeutic agents have not

shown any significant clinical effect that affects the AD patients’ behavior. This also proves that

any damage to the basal forebrain varies in the patients of AD. Some autopsy series shows this to

be upto 90%, but damage to the basal forebrain has been found less coherent by others, which

give the greatest challenge in its measurement. Nucleus basal portion of basal forebrain was kept

during this measurement process performed. As ante mortem markers of AD in less severely

impaired patients, the temporal horn and hippocampus might be useful.

Metabolic changes including microstructural loss is accompanied with atrophy, and can

be measured with MRI sequences which are sensitive to early changes. Inspite of all evidences,


temporal atrophy not happens to be accurate in serving as absolute diagnostic criteria for clinical

diagnosis of AD at MCI state. To lessen the false-positive diagnosis of AD, higher specificity is

needed. Medial temporal atrophy is devoid of this specificity to exclude other dementia. For

enhancing the correctness of structured markets, some other structural as well as nonstructural

measures are to be included in an algorithmic formula so that AD can be diagnosed.

The parietal atrophy along with medial temporal lobe atrophy on MRI carries positive

predictive value for the diagnosis of AD. 59 Amenestic MCI patients converted in just 19 months

on an average, to dementia. Those with both medial temporal atrophy (as rated visually45) and

abnormal CSF biomarkers had a fourfold higher risk of progression to dementia than patients

with either abnormality alone.

MRI based imaging is integral to the assessment of patients with AD. For more precise

diagnosis and measurement, structured MRI markets are used. Whole brain rates as well as

hippocampal rates are sensitive markers of progression of neurodegeneratin and are being used

and preferred today by doctors. Brain change structural evolution and its relationship with

nonstructural markers need to be further examined. Similarly longitudinal change studies in AD

patients who underwent clinical assessment can be of immense help to know about a

combination of markers which can be helpful in early diagnosis. Many algorithms claim that

they provide the correct market measure should also be put to test and eventually human ratings

replacement and tracing will thus be available. Animal and human markers for the progressions

of disease will be helpful for the correct information about the effects of drugs and their traits in

humans.


According to the American Academy of Neurology the role of MRI is to rule out

structural lesions in human brain. Studies of AD patients in prodrornal phase, is associated with

development of AD by entorhinal atrophy. It also shows the association of entorhinal cortex in

AD patients. MRI findings also confirmed the involvement of the entorhinal cortex and the

banks of the superior temporal sulcus (both related to functions of memory) in patients with

prodromal AD. Researchers failed to report any inter-rater reliability testing in four studies

(Namazi & Haynes 1994, Namazi et al . 1995,Sambandham & Schirm 1995, Tabloski et al .

1995, Arkin 1999). These case studies are limited. Yet these studies with experimental design

and truly descriptive details raise crucial questions, like the importance to stage patients and also

of a specific intervention. Seldom present in studies, these can be made to use in order to show

the importance of a theory to study such activities among AD patients. Conceptual framework

may be used as a guide to quantitative research or be generated by qualitative research.

Researchers did not identify a theoretical framework that subjected their decisions about

choice of an activity, or how the activity was used. In its place, the researchers alluded to a

theoretical justification. Some of the researchers chose theories that stressed upon the importance

in the AD patients about the environment.

It is without doubt that researchers have taken great interest to diagnose AD patients but

both the methodological problems and unclear findings are present along with the absence of

greater importance to gender, ethnic or even cultural differences. Complicating this is the issue

of sampling which often complicate the research of patients with AD. Therefore it is imperative


to have more experimental and quasi experimental designs for the furtherance of knowledge. It is

important to note that the diagnosis problems and profiling of AD has adversely affected the

worth of the samples. It is a truth that a really factual diagnosis is only possible with only one

way, an autopsy or a brain biopsy. It has been proved that MRI prediction method is 75 percent

accurate diagnosis of pre-confirmed disease diagnosis as well as to those with biomarker levels.

MRI tests to fully understand and measure the progression of mental impairment disease are

crucial because the new therapies to slow down neurodegenerative disease are undergoing

clinical trials. It is known that if diseases of mental impairment are recognized in the very early

stages, it can be beneficial to the patient and his family, in order to plan the future accordingly.

Today the research that is continuing in the MRI realm have given hopes to the

researchers that soon it can enhance the power to measure brain atrophy in order for a faster,

effective and economical diagnosis of mental impairments and to distinguish them from other

forms of diseases like dementia. But it should be noted that sometimes even MRI or CT scan are

found to be inconclusive by the physicians. In this case the physicians recommend tomography

or simply PET procedures which helps provide very sharp images of the activity of human brain

like the flow of blood, the consumption of oxygen and the use of glucose. PET helps to narrow

down the physicians understanding as it shows those aliments which are common the AD

disease.


Figure Legends


References

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use of mri in the diagnosis of a specified pathological condition of the brain

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