Mohamed El-Sirafy et al.

Clinical Feasibility of Diffusion-Weighted Magnetic Resonance Imaging Using 0.2 Tesla Machines in Differentiating Brain Infections from Brain Tumors: An Egyptian Study Mohamed Nasr I. El-Sirafy1, Mona A. Nada2, Khaled I. Newaem1, Ismail R. Aly3, Sherif E. Hegab1, Mohamed Ihab S. Reda1 Departments of Radiology1, Alexandria University; Neurology2, Cairo University; Neurology3, Alexandria University3

ABSTRACT Background: Differential diagnosis of brain abscesses versus cystic or necrotic tumors based on CT or MRI findings is unfortunately difficult. Objectives: Evaluate the clinical feasibility of DWI at low field (0.2 Tesla open magnet) MRI machines in differentiating brain infection from brain tumors (abscesses from necrotic or cystic brain tumors/encephalitis from diffuse gliomas) among Egyptian patients. Methods: This study was conducted on 25 Egyptian patients (13 females, 12 males with a mean age of 41) with MRI evidence of necrotic lesions and ring-shaped enhancement after contrast material and was examined with DWI open 0.2 Tesla imager. Results: Diffusion restriction was identified in 5 patients with intra-axial cystic lesions and diagnosed as having brain abscess differentiating them from cystic gliomas/cystic metastasis. In 9 patients, abnormal T2 and FLAIR hyperintensity with restricted diffusion in DWI were diagnosed as encephalitis rather than neoplastic lesions. Seven patients were diagnosed as having cystic intra-axial neoplasm where by DWI the cystic components of the lesions showed no diffusion restriction differentiating them from brain abscesses. Four patients were diagnosed as diffuse gliomas with no enhancement identified and on DWI, no restriction was detected excluding encephalitis. Conclusion: DWI provides a greater degree of confidence in differentiating brain infection from brain tumors (abscesses from necrotic or cystic brain tumors and encephalitis from diffuse gliomas) than conventional MRI. DWI on 0.2 Tesla MRI machines is capable in distinguishing brain infection from brain tumors if high field MRI machines are not available. (Egypt J. Neurol. Psychiat. Neurosurg., 2009, 46(2): 299-310) Key words: Magnetic resonance imaging; Diffusion-weighted; Brain tumor; Brain infection, low field (0.2 Tesla open magnet) MRI machines.

INRODUCTION Differentiating brain abscesses from necrotic or cystic tumors of the brain is a fundamental clinical issue as the strategies of their management and their prognosis differ completely. Unfortunately, this differentiation remains a diagnostic challenge for both neurologists and radiologists. Correct diagnosis of cystic brain lesions must be obtained before treatment can begin. Not only is the correct

diagnosis of cystic brain lesions crucial but also their early diagnosis. In fact, early identification of a brain abscess is essential as this potentially fatal lesion can be treated successfully by means of medical or surgical interference resulting in better prognosis. The differential diagnosis of brain abscesses versus cystic or necrotic tumors using computed tomography (CT) or conventional magnetic resonance (MR) imaging findings is unfortunately difficult1. Difficulties in the diagnosis of intracranial abscess are mainly due to the combination of

Correspondence to Mona Abdel Fattah, e-mail: [email protected]. Contact number: +20123911703

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indefinite clinical findings and similarities in the morphologic appearance of some intracranial mass lesions by CT and/or MRI, e.g. cystic gliomas, brain metastases2, 3 and non-tumor ring-enhancing brain lesions4. As regards clinical presentations, the classic triad of fever, headache and neurological deficit is rarely found in patients with brain abscess 5. Moreover, fever is only detected in less than 50% of cases6. On conventional MRI, the abscess center usually shows hypointensity relative to the brain parenchyma on TI-weighted images and hyperintensity on T2-weighted images. The abscess wall usually shows a ring of enhancement after contrast administration. However, these findings can also be seen in necrotic or cystic brain tumors 7. Diffusion-weighted imaging (DWI) provides image contrast different from that provided by conventional MR techniques as it provides a means to evaluate the diffusion properties of water molecules in tissue of the brain which may be substantially altered by diseases. According to Fick’s law, true diffusion is the net movement of molecules due to a concentration gradient. With MRI, molecular motion due to concentration gradients cannot be differentiated from molecular motion due to pressure gradients, thermal gradients, or ionic interactions. Therefore, when measuring molecular motion with DW imaging, only the apparent diffusion coefficient (ADC) can be calculated8. It has been used to study the normal brain 9 and various diseases such as ischemia, tumors, epilepsy, and white matter disorders.10,11 In developing countries, the majority of available MRI units are still low magnetic field MRI e.g. 0.2 and 0.3 Tesla machines. To our knowledge, most of the studies previously done to differentiate between brain abscesses and tumors used either 1.5 or 3 Tesla MRI machines.12-15 Therefore, this study aimed to evaluate the clinical feasibility of diffusion-weighted imaging (DWI) at low field (0.2 Tesla open magnet) MRI machines in differentiating brain infection from brain tumors (abscesses from necrotic or cystic brain tumors and encephalitis from diffuse gliomas) among Egyptian patients.

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SUBJECTS AND METHODS Patients: This study was conducted on 25 Egyptian patients including 13 females and 12 males during two years duration: starting from 2006 through 2008. The age of our patients ranged from 3 to 79 years with a mean age of 41. All patients were subjected to full history taking, thorough clinical and neurological examination. Patients with MR imaging evidence of necrotic lesions and of ring-shaped enhancement after the injection of contrast material were examined with DW MRI on open 0.2 Tesla imager. Magnetic resonance imaging: Conventional MRI examination of the brain was performed for all patients on 0.2 T scanner (Siemens, Magnetom Open Viva, Germany) and 0.2 T scanner (Hitachi, Airis Mate, Tokyo, Japan) in private Radiodiagnosis centers in Egypt. Screening patients for any contraindications to the MRI examination, such as cardiac pacemakers was done. The contrast material used in the study was Gadolinium diethylene triamine pentacetic acid (Magnevist) at dose 0.2 ml/Kg body weight with no reactions detected to contrast material injection in our study. The head coil was used as the receiver coil. Each examination included: Pre-contrast series including axial and sagittal T1-weighted spin echo (SE), axial and coronal T2-weighted turbo spin echo (TSE) and axial FLAIR. Post-contrast series included axial, coronal and sagittal T1-weighted spin echo (SE). The following parameters were utilized: Slice thickness: 6 mm, Interslice gap: 0.6 mm. Field of view (FOV): 230-240 mm2, RFOV: 80%. Number of signals averaged (NSA): 2 For T1W sequences: TR= 350-600 msec; TE= 10-15 msec. For T2W sequences: TR= 4000-8000 msec; TE= 100- 135 msec; TSE Factor = 11. For FLAIR: TR= 5000-11000 msec; TE= 90-140 msec. Diffusion-weighted MRI: The diffusion-weighted MRI images were obtained for all patients in our study with a single

Mohamed El-Sirafy et al.

shot, gradient-echo, echo-planar pulse sequence with diffusion gradient b values of 0 and 800-1000 s/mm2, along three orthogonal axes (x, y, and z directions) over 22 axial sections, TR= 5072; number of sections, 16-22; section thickness, 5 mm; intersection gap; 1 mm. Final diagnosis was reached either by therapeutic response to antibiotics (in 14 patients), surgical findings and histopathological examination, or a consensus of clinical and imaging modalities (in 11 patients).

RESULTS In the present study, diffusion restriction by DWI were identified in five patients with intra-axial cystic lesions by conventional MRI and were diagnosed as having brain abscess differentiating them from cystic gliomas and cystic metastasis. The size of all abscess contents appears to be slightly larger on DWI than on conventional MR images. Those five patients included 3 males and 2 females with their ages ranging from 23 to 72 years with a mean age of 41.5. The clinical manifestations of patients with brain abscess in the present study are shown in table (1). In nine of our patients, abnormal T2 and FLAIR hyperintensity in the frontal, temporal, and parietal regions with restricted diffusion in DWI were found setting the diagnosis of encephalitis rather than neoplastic lesions. Those patients

included five females and four males with their age ranging from three to 50 years with the mean age 26.5 and presented with the clinical findings shown in table (2). In the present study, seven patients were diagnosed as having cystic intra-axial neoplasm where the conventional MRI revealed intraaxial cystic lesions, displaying T1 hypointensity, T2 hyperintensity and showed intense peripheral enhancement after contrast injection. On DWI, the cystic components of the lesions showed no diffusion restriction diagnosing them as neoplasm and differentiating them from brain abscesses (which showed diffusion restriction). Two of those patients were grade II cystic astrocytoma, three were glioblastoma multiform, and two were cystic metastasis from cancer breast as shown in table (3). Four patients in the present study were diagnosed as having diffuse gliomas, in which their conventional MRI revealed ill-defined infiltrative lesions. All showed T1 hypointensity, T2 and FLAIR hyper-intensity with no enhancement identified after contrast injection. The lesions were mimicking encephalitis (herpetic type) but on DWI, no restriction was detected in the four patients thus diagnosing diffuse gliomas and excluding encephalitis. The clinical manifestation, age and sex distribution in those patients is shown in table (4).

Table 1. Clinical Presentation and DWI Findings in Patients with Brain Abscess. Sex

Clinical presentation

Diagnosis

43

M

Headache, neck rigidity and right sided weakness

Brain abscess related to medial aspect of trigone and body of left lateral ventricle

23

F

RHD, fever, headache and confusion

Left high parietal abscess

44

M

Fever, headache, confusion

Left frontal abscess

42

M

Fever, headache and confusion, fits

Left temporoparietal abscess

72

F

Fever, left hemiparesis and fits

Right parietal bilocular abscess

DWI Restricted diffusion

Age

M= Male, F= Female, RH= Rheumatic heart disease, DWI=Diffusion weighted imaging

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Table 2. Clinical Presentation and DWI findings in Patients Presenting with Encephalitis. Age

Sex

Clinical presentation

42

M

Fever, confusion and fits

41

F

Fever and fits

48

F

Fever, confusion and fits

20

F

45

M

3

F

Disturbed consciousness and fever

36

M

Fever, confusion and fits

50

F

Fever, confusion and fits

50

M

Disturbed consciousness, fever and fits

Fever, fits and disturbed consciousness Fever and acute frontal lobe manifestation

Diagnosis

DWI

Right temporal herpetic encephalitis Early left medial temporal herpetic encephalitis Bilateral patches of herpetic encephalitis, at temporal and inferior frontal lobes, more at left temporal lobe Left temporal herpetic encephalitis with hemorrhagic focus Bilateral frontal mainly cortical encephalitic patches Bilateral scattered patches of encephalitis, notably involving the basal ganglia

Restricted

Left temporoparietal herpetic encephalitis

Restricted

Bilateral temporal patches of herpetic encephalitis Bilateral patches encephalitis, more at right temporal lobe

Restricted Restricted Restricted Restricted Restricted

Restricted Restricted

M= Male, F= Female, DWI=Diffusion weighted imaging

Table 3. Clinical presentation and DWI in patients with intra-axial cystic neoplasms. Age

Sex

Clinical presentation

45

M

Signs of increased ICP and right sided weakness

Left high parietal cystic astrocytoma

32

F

Epilepsy and signs of increased ICP

Right temporal cystic astrocytoma

40

F

57

M

50

M

45

F

54

F

Signs of increased ICP and left sided weakness Signs of increased ICP, right sided weakness and seizures Signs of increased ICP, right sided weakness and seizures Signs of increased ICP and left hemiparesis Signs of increased ICP

Diagnosis

Right high parietal GBM Left frontal cortical and sub-cortical GBM (mid & high convexity levels) Left parietal cortical and sub-cortical GBM (mid & high convexity levels) Cystic metastasis from breast cancer Cystic metastasis from breast cancer

DWI No restriction No restriction No restriction No restriction No restriction No restriction No restriction

M= Male, F= Female, DWI=Diffusion weighted imaging, ICP=Intracranial pressure, GBM= glioblastoma multiform

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Table 4. Clinical Presentation and DWI in Patients with Diffuse Gliomas. Age

Sex

Clinical presentation

20

F

Epilepsy and right hemiparesis

53

M

Epilepsy

48

M

Right lower limb monoparesis

43

M

Left lower limb weakness and headache

Diagnosis

DWI

Left temporoparietal diffuse glioma, involving the left cerebral peduncle and left side of the pons (gliomatosis cerebri)

No restriction

Left temporal low grade glioma (gliomatosis cerebri) Left para-sagittal high frontal low grade glioma (diffuse astrocytoma) Right high posterior parietal low grade glioma

No restriction No restriction No restriction

M= Male, F= Female, DWI=Diffusion weighted imaging

(A)

(B)

(C)

(D)

(E)

(F)

A 43 years old male patient presented with headache, neck rigidity and right sided weakness: Axial T2 W (A), axial FLAIR (B), axial T1 (C), and post contrast axial T1 W (D) MR images revealed bilocular intra-axial

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marginally enhancing cystic lesion related to the medial aspect of trigone and body of left lateral ventricle with a small intraventricular component. The lesion showed restricted diffusion being hyperintense on the axial DWI (E) and hypointense on the axial ADC image (F). Diagnosis: Brain abscess.

(A)

(B)

(C)

(D)

(E)

(F)

A 42 years old male patient presented with fever, confusion and fits. Axial T2 W (A), axial FLAIR (B), axial T1 W (C), post contrast coronal T1 W (D) and coronal T2 W (E) MR images revealed swollen right temporal lobe

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displaying T1 hypointensity and T2 and FLAIR hyperintensity with no significant enhancement. The lesion was hyperintense on the coronal DWI (F), denoting restricted diffusion. Diagnosis: Right Temporal Herpetic Encephalitis ruling out the possibility of diffuse glioma.

(A)

(B)

(C)

(D)

(E)

(F)

A 53 years old male patient presented with epilepsy since six months: Axial FLAIR (A), coronal T2 (B), pre contrast (C) and post contrast (D) axial T1 W MR images revealed left temporal intra axial infiltrative space

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occupying lesion, displaying T1 hypointensity, T2 and FLAIR hyperintensity with no enhancement. It showed no diffusion restriction on axial DWI (E, F). Diagnosis: Low Grade Diffuse Glioma ruling out possibility of herpetic encephalitis.

(A)

(B)

(D)

(C)

(E)

A 45 years old male patient presented with signs of increased ICP and right sided weakness: Axial T2 (A), axial T1 (B), post contrast axial (C) and coronal (D) T1 W MR images revealed a well defined left high parietal intraaxial cystic space occupying lesion, displaying T1 hypointensity, T2 hyperintensity and intense peripheral enhancement. Grade II perifocal edema is noted with associated mass effect. No diffusion restriction identified on the axial DWI (E). Diagnosis: Cystic Astrocytoma ruling out the possibility of abscess.

DISCUSSION There is convincing evidence to suggest that DW MR imaging has become necessary tool for the detection and characterization of a variety of cerebral disease states and is substantially more sensitive than regular T1- and T2-weighted or FLAIR MR imaging and far more sensitive than CT.

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Brain abscess can be a lethal condition if appropriate treatment is delayed. Thus, early diagnosis of brain abscess is needed. By conventional MRI, the typical brain abscess has low signal intensity on T1-weighted images, high signal intensity on T2-weighted images, and ring enhancement after contrast medium administration. However, cystic or necrotic brain tumors can have the same clinical picture, and differentiating them from abscesses can be very difficult. Accordingly, it

Mohamed El-Sirafy et al.

can be difficult to reach a differential diagnosis of ring-enhancing intracranial mass lesions on the basis of clinical symptoms and conventional MRI. Pus in the cavity of the brain abscess consists of bacteria, inflammatory cells, necrotic tissue and highly viscous protienaceous exudates while cystic or necrotic tumors consist of necrotic tumor tissue debris, few inflammatory cells and serous fluid. Pyogenic brain abscess has been reported to have markedly increased signal intensity on DW images and markedly decreased signal intensity on ADC maps, while the opposite happens in necrotic tumors. This can be explained by high viscosity and cellularity of pus with consequent restriction of the diffusion of water molecules. In our study, diffusion restriction was identified in five patients with brain abscesses differentiating them from necrotic brain tumors. This goes in concordance with other studies done on 1.5 Tesla MRI which stated that signal intensity of the abscess cavity is markedly higher and the ADC ratios are lower than those of necrotic tumors on DWI.16,17 Ebisu et al.18 performed in vitro DW imaging of aspirated pus, as well as ADC measurements. The pus imaged in vitro showed high signal intensity on DWI and low ADC values, similar to the results of the in vivo study. They concluded that the pus structure itself is responsible for the low ADC values, and that the heavily impeded water mobility of pus may be related to its high cellularity and viscosity. The presence of large molecules, such as fibrinogen, also may play a key role in restricting the diffusion of protons in pus.19 In the current study, nine patients had encephalitis where restricted diffusion on DWI was evident in all of them. Six of them were diagnosed to be herpetic, in which the presence of diffusion restriction helped in differentiating them from infiltrative neoplastic lesions. The restricted diffusion is explained by cytotoxic edema in tissues undergoing necrosis. This goes with other studies done on 1.5 Tesla MRI that stated that DWI may aid in distinguishing herpes lesions from infiltrative temporal lobe tumors because the ADCs of herpes lesions are low while the ADCs of various tumors are elevated or in the normal range.20-22 To date, MRI has principally served the role of showing the neoplasm, helping distinguish tumors from other pathologic processes, and depicting basic

signs of tumor response to therapy, such as change in size and degree of contrast material enhancement. Diffusion-weighted (DW) imaging may allow the cellularity of tumors to be graded non-invasively; because cells constitute a relative barrier to water diffusion, compared with extracerebral space. Tumors that are more cellular would be expected to show lower ADC values than tumors that are less cellular. Also, DWI has a number of applications with regard to characterization of tumors and assessment of tumor response to therapy. Perfusion and DW MR Imaging are providing insights into tumor behavior that are not available from conventional MRI and will likely be more important for assessment of tumor response to therapy than for diagnosis.23 In the present study, the cystic components of all cystic gliomas and metastasis showed no restricted diffusion on DWI, differentiating them from clinically possible brain abscesses which showed diffusion restriction. Desbarats et al.24, also stated that it is often impossible to reach a differential diagnosis between brain abscesses and cystic or necrotic brain tumors using conventional MRI and that DWI is a useful tool to explore water diffusion and to make this differential diagnosis possible. Other investigators stated that conventional MRI has limited application and DWI is a good method for differentiating brain abscess from cystic or necrotic brain tumors in most cases. However, exceptions exist, and care should be taken when unusual presentation is encountered.17 On the contrary, Park et al.25 reported two cases of cystic or necrotic metastatic brain lesions with markedly high signal intensity on DWI. Surgery disclosed that the cysts had a thick and creamy necrotic content similar to pus. The infiltrative and low grade gliomas in the current study also showed no diffusion restriction, differentiating them from herpetic encephalitis. Such differentiation was impossible by the conventional MRI. This agrees with other investigators who stated that low grade and infiltrative gliomas showed no evidence of restricted diffusion on DWI. 21,22 Hamon et al.26 reported as well that, regarding temporal lobe lesions, the DWI can contribute to the differential diagnosis between herpetic encephalitis and low grade diffuse glioma, whose ADC is generally

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identical or higher compared to the healthy parenchyma (i.e. no diffusion restriction). 10.

Conclusion Diffusion-weighted imaging is useful in providing a greater degree of confidence in differentiating brain infection from brain tumors (abscesses from necrotic or cystic brain tumors and encephalitis from diffuse gliomas) than conventional MRI and seems to be a valuable diagnostic tool. DWI on 0.2 Tesla MRI machines is capable in distinguishing brain infection from brain tumors if high field MRI machines are not available.

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‫الولخص العربى‬ ‫تقيين دور التصىير باستخذام الرنين الوغناطيسى التخللى على جهاز ‪ 0.2‬تسال‬ ‫فى التوييس بين أفات الوخ االتهابية و أورام الوخ‪ -‬دراسة هصرية‬

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