RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA

BANGALORE
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

Name of the Candidate Dr. RAJESH POOSARLA

S/o P.CHITTI BABU,
and Address DOOR NO. 49-7-10/3, LALITHANAGAR,
1 VISAKHAPATNAM-530016,
(in Block Letters) ANDHRA PRADESH.
2 Name of the Institution J.J.M. MEDICAL COLLEGE,
DAVANGERE – 577 004.

3 Course of the Study and Subject POSTGRADUATE

M.D. IN RADIO-DIAGNOSIS

4 Date of Admission to Course 29th MAY 2010

5 Title of the Topic “ROLE OF MRI IN THE
EVALUATION OF RING ENHANCING
LESIONS IN BRAIN IN CORELATION
WITH MR SPECTROSCOPY”.

6 BRIEF RESUME OF THE INTENDED WORK

6.1 Need for the Study:
During the last century, central nervous system (CNS) imaging has witnessed
a revolution with advances that have impacted all aspects of neuroscience practice in
general and the management of intra-axial brain tumors in particular. Intraaxial brain
lesions present several imaging challenges. The role of imaging is no longer limited
to merely providing anatomic details. Sophisticated magnetic resonance (MR)
imaging techniques allow insight into such processes as the freedom of water
molecule movement, the microvascular integrity and hemodynamic characteristics,
and the chemical makeup of certain compounds of masses. The role of the most
commonly used advanced MR imaging techniques-perfusion imaging, diffusion-
weighted imaging, and MR spectroscopy-in the diagnosis and classification of the
most common intraaxial brain lesions in adults is explored. These lesions include

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primary neoplasms (high- and low-grade), secondary (metastatic) neoplasms,
lymphoma, tumefactive demyelinating lesions, abscesses, and encephalitis.
Application of a diagnostic algorithm that integrates advanced MR imaging features
with conventional MR imaging findings may help the practicing radiologist make a
more specific diagnosis for an intraaxiallesion.1

Infective pathologies were the most common etiology for multiple enhancing
lesions of the brain in India. Tuberculosis was the commonest infective pathology,
followed by neurocysticercosis. Neoplastic diseases were common non-infective
causes. In majority, brain lesions were metastatic manifestation of a systemic
neoplastic disorder.2

Brain abscesses are potentially fatal lesions that may be treated successfully
by medical or surgical intervention or both. Uniformly thin and spherical rims are
characteristic of cerebral abscesses. Nevertheless,a variety of tumors, including
gliomas and metastases, can present a similar appearance and both frequently are
treated surgically, regardless of the MR findings. Many abscesses, however, can be
aspirated with CT or MR guidance and successfully treated with antibiotic therapy.
Therefore, it would be beneficial to patients to establish an early and correct
diagnosis.3

The Introduction of MAGNETIC RESONANCE IMAGING (MRI) has

created many important advances in the detection and characterization of brain
lesions and is considered to be the state of the art technology in the evaluation of
the brain. The detection rate of most types of brain lesions by MRI exceeds 90%,
compared to 77% for CT - without the invasiveness or risk of iodinated intravenous
contrast agents or the inherent problem of the radiation effect of X-rays. These
safety features make MRI especially advantageous for the pediatric and elderly
populations.

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 MRI’s clinical advantage in early detection of disease is visually
demonstrated as unmistakable contrast between gray and white matter and tumor
ischaemia/infarct, edema, MS plaques, infection/abscess and hemorrhage.
Contributing to this is MRI's inherent sensitivity as well as its capability to directly
image in any place without reformatting, and to be unimpeded or undistorted by
bony structures.
Magnetic resonance imaging is an excellent method for anatomical and
structural diagnosis of the brain, but it does not provide functional or metabolic
information.
Magnetic resonance spectroscopy (MRS) allows the non-invasive
measurement of selected biological compounds in vivo .Feasibility was first
demonstrated in humans in the mid-1980s. Since that time, much experience has
been accumulated with the use of MRS in both research and clinical applications.
Proton spectroscopy has been recognized as a safe and noninvasive diagnostic
method that, coupled with magnetic resonance imaging techniques, allows for the
correlation of anatomical and physiological changes in the metabolic and
biochemical processes occurring within previously determined volumes in the brain.
MR spectroscopy is a potential tool for differential diagnosis between brain
abscesses and non-infectious lesions such as primary brain tumor, lymphoma, brain
metastasis, and tuberculoma. Magnetic resonance spectroscopy (MRS) provides
information about the possible extent and nature of changes on a routine MRI scan
by analyzing the presence and/or ratio of tissue metabolites such as NAA, creatine
, choline, and lactate etc.
Widespread usage of faster MRS applications with higher signal-to-noise
ratio (SNR) and spatial resolution, allows us to detect functional metabolic changes,
which provides more data to understand the exact nature of the tumour and the
morphological and physiological changes occurring in the surrounding brain
parenchyma. Longitudinal studies have demonstrated that HMRS is useful in
monitoring disease progression and treatment effects. MR spectroscopy also has a
prognostic implication.4

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 Follow-up assessment of cerebral tumors is another promising field for MR
spectroscopy. Increases in size and contrast enhancement are typical findings in
tumor progression but also reflect therapy-induced changes. The same is true for
postoperative changes. There are other specific changes in MR spectra due to
abscesses; these include the occurrence of resonance representing acetate, lactate,
pyruvate, and succinate.

Thus a study design to evaluate the contribution of imaging science towards

the evaluation and diagnosis of ring enhancing lesions of brain.

6.2 Review of Literatures:

Gadolinium contrast imaging has become the "gold standard" in the
primary evaluation of brain tumor of all types, benign or malignant; post-operative
recurrences; differentiating edema from tumor foci; metastatic brain disease; and
those pathologies requiring the detection of very small masses.
The various ring enhancing lesions in brain on gadolinium injection are :
1. Primary brain tumor (high grade lesions)
2. Metastasis (especially post chemotherapy)
3. Abscess
4. Multiple sclerosis
5. Resolving hematoma (10-21 days)
6. Tuberculoma
7. Radiation necrosis
8. Postoperative changes
9. Aneurysm
At MRI, the toxoplasma lesions are multiple, commonly located in the deep
central nuclei, posterior fossa or lobar at the gray-white matter junction, with
prominent associated mass effect and edema and typically show intense rim
enhancement (ring enhancing ) after gadolinium administration. The toxoplasma
lesions are hyperintense on T2- and hypointense on T1-weighted
sequences. However, unlike water diffusion in the center of a pyogenic abscess,

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water diffusion is not restricted in the center of the toxoplasma
abscess. Spectroscopy is characterized by a predominant lipid peak. 5

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 Magnetic resonance imaging and magnetic resonance spectroscopy were
analyzed retrospectively in 62 patients with ring enhancing intra cerebral lesions,
including 20 gliomas in 18 metastatic tumours, 16 brain inflammations and 8
radiation damages. The appearance rate of lactate , choline, NAA were calculated.
The study was concluded that 2D CSI 1 HMRS is very useful in the differential
diagnosis of ring enhancing intracerebral lesions and the combined application of
MRI and MRS has a higher diagnostic value.6
In a study consisting of 111 patients 44 patients with high-grade and 14 with
low-grade primary neoplasms, 24 with abscesses, 12 with lymphoma, 11 with
TDLs, five with metastases, and one with encephalitis who had undergone
conventional and advanced MR imaging.. Accuracy, sensitivity, and specificity of
the strategy, respectively, were 90%, 97%, and 67% for discrimination of neoplastic
from non neoplastic diseases, 90%, 88%, and 100% for discrimination of high-grade
from low-grade neoplasms ,and 85%, 84%, and 87% for discrimination of high
grade neoplasms and lymphoma from low-grade neoplasms.7
Eleven children (mean age, 9 years) being examined for brain tumors
underwent MR imaging that revealed indeterminate criteria of enhancement, mass
effect, and prolonged T1 andT2 signal. MR spectroscopy was then used to
distinguish radiation necrosis from tumor in one patient, differentiate residual tumor
from scarring in two patients, document early treatment response in three patients,
and discriminate benign from malignant masses in five patients. In 10 of the 11
patients, spectra were successfully acquired. Based on the chemical analysis of the
indeterminate area shown on MR imaging, clinical impact was achieved in these 10
patients. When MR imaging is indeterminate in evaluating pediatric brain tumors,
MR spectroscopy can provide objective neurochemical information, thereby
altering treatment.8
Twenty seven patients with a total of 33 pyogenic brain abscesses and three
patients with a total of 12 tuberculous abscesses were evaluated with in vivo MR
spectroscopy and MT MR imaging. All 27 patients with pyogenic brain abscesses
had lipid and lactate levels of 1.3 ppm and amino acid levels of 0.9 ppm with or

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without the presence of succinate, acetate, alanine, and glycine, while the three
patient with tuberculous abscesses showed only such lipid and lactate levels. It
might be possible to differentiate tuberculous abscesses from pyogenic abscesses by
using MT MR imaging and in vivo MR spectroscopy, which could be of value in
influencing the management of such cases.9

MR imaging and in vivo single-voxel proton MR spectroscopic data obtained

from 75 patients with brain abscesses were retrospectively analyzed. It is possible
to differentiate anaerobic from aerobic or sterile brain abscesses on the basis of
metabolite patterns observed at in vivo proton MR spectroscopy. This information
may be useful in facilitating prompt and appropriate treatment of patients with these
abscesses.10

Ten patients with SELs caused by neurocysticercosis (n = 6) or tuberculosis

(n = 4) were examined by proton magnetic resonance spectroscopy. Tuberculomas
had a high peak of lipids, more choline, and less N-acetylaspartate and creatine. The
choline/creatine ratio was greater than 1 in all tuberculomas but in none of the
cysticerci. Magnetic resonance spectroscopy differentiates SELs caused by
cysticercosis or tuberculosis and may avoid brain biopsies or unnecessary
antituberculosis treatments.11

MR spectroscopy findings in a case of neurocysticercosis are presented. A

combination of elevated lactate, alanine, succinate, and choline levels and reduced
levels of N-acetylaspartate and creatine in a cystic intraaxial lesion in the brain
helped in characterizing the lesion. To our knowledge, the short echo point resolved
spectroscopic sequence (PRESS) spectrum of neurocysticercosis, as described in
our case, has not been reported before.12
Intracranial inflammatory lesions consisting mainly of tuberculomas (n = 28),
neurocysticercosis (NCC) (n = 10), and non-specific inflammatory granulomas (IG)
(n = 22) were evaluated with proton MRS. While the presence of lipid can be used
for differentiating tuberculomas from both non-specific IG and NCC, the extremely
low levels of metabolites together with a poor signal/noise ratio could itself act as a
marker for NCC.13

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 Fifty-one patients with intracranial cystic lesions (21 abscesses, 20 gliomas,
3 hydatid cysts, 3 arachnoid cysts, 1 case each of glioependymal cyst,
xanthogranuloma, infarction and acoustic neuroma) were evaluated with
conventional MR imaging and in vivo PMRS. In vivo PMRS accurately predicted
the pathology in 92% of the cases. We conclude that in-vivo PMRS complements
imaging in better characterization of cystic intracranial mass lesions.14

In a prospective clinical study including 120 patients with intracranial lesions

reported a diagnostic accuracy of 85.6% with proton MR spectroscopy .Moreover,
proton MR spectroscopy can also provide clues to the cause of an abscess, and
consequently, its likely response to medical or surgical treatment. These authors
found that the diagnostic accuracy, sensitivity, specificity, and the positive and
negative predictive values of conventional MR images were 61.4, 61.9, 60.9,
59.1,and 63.3%, respectively, while the respective rates for proton MR spectroscopy
were 93.2, 85.1, 100, 100, and 88.5%.15

In a cooperative study involving six clinical MR centers, localized 1H MR

spectroscopy was used to characterize untreated metastatic brain tumors (40 cases,
45 lesions). Cubic volumes (3.4 or 8 cm3) filled for more than 50% by metastatic
brain tissue were examined by single-voxel double spin echo MRS 1H MR
spectroscopy, although not suited to recognize the primary tumor of metastases,
could serve as a clinical test for excluding (metastatic) tumor as cause of solitary
focal brain disorders that are hard to diagnose with current imaging methods. 16

In a study in 2001 with ten patients with acute contrast enhancing multiple
sclerosis lesions,10 patients with chronic lesions and 10 healthy subjects were
investigated with a 1.5 tesla whole body system, using a STEAM sequence with
metabolite–nulling and volume saturation . NAA was significantly reduced in both
the acute and the chronic multiple sclerosis compared with the controls .17

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 Seventy-two lesions in 56 patients were examined using a combined MR
imaging and MR spectroscopy protocol (point-resolved spectroscopy, TE = 135
ms). Signal intensities of cholines, creatines, N-acetyl aspartate, and the presence of
lactate and lipid resonances were correlated to final diagnoses established by clinical
and MR imaging follow-up, positron emission tomography studies, or
biopsy/surgery.: Metabolic information provided by proton MR spectroscopy is
useful for the differentiation of neoplastic and non neoplastic brain lesions after
stereotactic radiotherapy of brain tumors.18

6.3 Objectives of the Study:

• To differentiate neoplastic from non neoplastic brain lesions using
conventional and advanced MR imaging techniques.
• To establish a differential diagnosis of the various ring enhancing lesions on
conventional MRI.
• To study the role of MR spectroscopy in the evaluation of various ring
enhancing lesions in the brain with a single voxel proton mr spectroscopy

7. MATERIALS AND METHODS

7.1 Source of Data:
The main source of data for the study are patients from the following teaching
Hospital attached to Bapuji Education Association, J.J.M. Medical College,
Davangere.

1. Bapuji Hospital.
2. Chigateri General Hospital.
3. S.S. Institute of Medical Sciences & Research Centre

Appropriate MRI sequences and multiplanar imaging will be performed for

every patient

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7.2 Method of Collection of Data (including sampling procedure if any):
All patients referred to the department of Radio diagnosis with clinically
suspected cerebral ring enhancing lesions in a period of 2 years from Nov 2010 to
November 2012 will be subjected for the study.

Initially a minimum of 25 cases are intended to be taken up, however the scope
of increasing the number of cases exists depending upon the availability within the
study period.

Inclusion Criteria:
The study includes
• All cerebral ring enhancing lesions detected on contrast MR studies are taken
up retrospectively.
• All patients with incidentally diagnosed ring enhancing lesion by CT.
• Cases of all age groups irrespective of sex

Exclusion Criteria:
The study will exclude
• Patient having history of claustrophobia.
• Patient having history of metallic implants insertion, cardiac pacemakers and
metallic foreign body insitu

Duration of study : 2 years

Data Analysis : Diagnostic validity test are used.

7.3 Does the study require any investigations or interventions to be conducted

on patients or other humans or animals? If so please describe briefly.
YES.
The study is mainly based on investigations as Radiology itself is a tool of
Investigation. . The study involves only humans. Informed consent would be taken
after explaining about and before any procedure. Routine investigations, laboratory
investigations, Ultrasonogram and CT.

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7.4 Has ethical clearance been obtained from your institution in case of 7.3?
Yes.
Ethical clearance has been obtained from the Research and Dissertation
Committee/ Ethical Committee of the institution for this study

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8 LIST OF REFERENCES
1. Al-Okaili RN, Krejza J, Wang S, Woo JH, Melhem ER. Advanced MR Imaging
Techniques in the Diagnosis of Intraaxial Brain Tumors in Adults. Radio
Graphics 2006 October;26:S173-S189.
2. Garga RK, Desaia P, Karb M, Kara AM. Multiple ring enhancing brain lesions
on computed tomography: An Indian perspective 2008March;266(1):92-96.
3. Desprechins B, Stadnik T, Koerts G, Shabana W, Breucq C. Michel Osteaux
Use of Diffusion-Weighted MR Imaging in Differential Diagnosis Between
Intracerebral Necrotic Tumors and Cerebral Abscesses. AJNR Am J
Neuroradiol 1999 August;20: 1252–1257.
4. Bulakbasi N. Clinical applications of proton MR spectroscopy in the diagnosis
of brain tumours. Spectroscopy 2004; 18(2):143-153.
5. Amit A, Arvind B, Sangole VM, Brij SR. Multiple ring enhancing lesions in an
immunocompetent adult. J Global Infectious Disease 2010Sep–Dec;2(3):313-
314.
6. Kuangfei, Wangfei et al. Magnetic Resonance spectroscopy of ring enhancing
intracerebral lesions. Acad J Sec Mil Med Univ 2006Sep;27(9):pg.
7. Al-Okaili RN, Krejza J, Wang S, Woo JH, Melhem ER. Advanced MR imaging
techniques in the diagnosis of intraaxial brain tumors in adults. Radiographics
2006Oct;26(1):S173-89.
8. Norfray JF, Tomita T, Byrd SE, Ross BD, Berger PA, Miller RS. Clinical impact
of MRspectroscopy when MR imaging is indeterminate for pediatric brain
tumors. AJR Am J Roentgenol. 1999 Jul;173(1):119-25.
9. Gupta RK, Vatsal DK, Husain N, Chawla S, Prasad KN, Roy R, et al. Husain
Differentiation of tuberculous from pyogenic brain abscesses with in vivo proton
MR spectroscopy and magnetization transfer MR imaging. M.AJNR Am J
Neuroradiol. 2001 Sep;22(8):1503-9
10. Garg M, Gupta RK, Husain M, Chawla S, Chawla J, Kumar R, et al. Etiologic
categorization with in vivo proton MR spectroscopy. Radiology.2004 Feb;230
(2):519-27. Epub 2003 Dec 29.

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11. Javier PE, Martinot, Carlos, Garcia, Hector H, Alvarado, et al. Differential
Diagnosis Between Cerebral Tuberculosis and Neurocysticercosis by Magnetic
Resonance Spectroscopy Journal of Computer Assisted Tomography: 2005
January/February;29(1):112-114.
12. Sameer P, Alexander L, Helmuth G, Claudia LR., Barbaros EMR. Spectroscopy
in Neurocysticercosis. J Computer Assisted Tomography: Neuroradiology:
Case Report 2001Nov./Dec.;25(6):950-952.
13. Jayasundar R, Singh VP, Raghunathan P, Jain K, Banerji AK. Inflammatory
granulomas: evaluation with proton MRS. 1999May;12(3):139-144.
14. Shukla-Davea A, Royd RKR, Husaine N, Paulb L, Venkatesha SK, Rashidf MR,
et al. Prospective evaluation of in vivo proton MR spectroscopy in
differentiation of similar appearing intracranial cystic lesions
2001Jan.;19(1):103-110.
15. Fountas KN, Kapsalaki EZ, Gotsis SD, Kapsalakis JZ, SmissonHF III, Johnston
KW, et al: In vivo proton magnetic resonance spectroscopy of brain tumors.
Stereotact Funct Neurosurg 2000;74:83–94.
16. Sijens PE, Knopp MV, Brunetti A, Wicklo K, Alfano B, Bachert P, et al.
Spectroscopy in Patients with Metastatic Brain Tumors: A Multicenter Study
Magnetic Resonance in Medicine 1995June;33(6):818–826.
17. Mader, Seeger U, Weissert R, et al. Proton MR spectroscopy with metabolite –
nulling reveals elevated macromolecules in acute multiple sclerosis brain
2001;124:953-961.
18. Schlemmer HP, Bachert P, Herfarth KK, Zuna I, Debus J, Kaick GV. Proton
MR Spectroscopic Evaluation of Suspicious Brain Lesions After Stereotactic
Radiotherapy. Am J Neuroradiol 2001;22:1316-1324.

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9 Signature of Candidate

10 Remarks of the Guide Informative study. Useful in narrowing the

diagnosis of various ring enhancing lesions in
brain.
11 Name and Designation of
(in block letters)
11.1 Guide
Dr. JEEVIKA M.U.M.D.
READER,
DEPARTMENT OF RADIO-DIAGNOSIS,
J.J.M. MEDICAL COLLEGE,
DAVANGERE – 577 004.

11.2 Signature

11.3 Co-Guide (if any)

11.4 Signature

11.5 Head of Department Dr. PRAMOD J SETTY M.D.,

PROFESSOR AND HEAD,
DEPARTMENT OF RADIO-DIAGNOSIS,
J.J.M. MEDICAL COLLEGE,
DAVANGERE – 577 004.

11.6 Signature

12 12.1 Remarks of the

Chairman and Principal

12.2 Signature

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