Role of MR Spectroscopy and Diffusion Weighted Techniques in Discrimination between Capsular Stage Brain Abscesses, Necrotic and Cystic Brain Lesions

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1 Med. J. Cairo Univ., Vol. 80, No. 1, December: , Role of MR Spectroscopy and Diffusion Weighted Techniques in Discrimination between Capsular Stage Brain Abscesses, Necrotic and Cystic Brain Lesions MOHAMED A. HASSAAN, M.D.; KAREEM M. MUSA, M.D.; IHAB I. ALI, M.D. and AMRO M. SAFWAT, M.D.* The Departments of Radiodiagnosis and Neurosurgery*, Faculty of Medicine, Cairo University Abstract Purpose: The aim of this study was to compare MRS findings and those of DWI with biopsy results to determine which technique is more effective in discriminating between abscesses, cystic and necrotic brain lesions. Patients and Methods : Fifty patients (33 males & 17 females) having intracranial marginally enhancing cystic space occupying lesions on CT or conventional MRI, were further evaluated with DWI and MRS. Results : This study included 18 patients with abscess and 32 patients with cystic or necrotic tumours. The correct diagnosis of brain abscess were made in 15 patients by DWI while the correct diagnosis were made in 14 patients by MRS. On the other hand, the correct diagnosis of cystic or necrotic tumour were made in 31 patients by DWI while the correct diagnosis were made in 30 patients by MRS. The sensitivity, specificity, PPV and NPV for DWI were 96.88%, 83.33%, 91.18%, 93.75% respectively, while they were 93.75%, 77.78%, 88.24%, 87.5% for MRS. Conclusion : Comparing DWI and MRS to differentiate brain abscesses from cystic or necrotic brain tumours show that DWI is more accurate, requires less imaging time and is also easier to interpret. Key Words: Brian abscess Cystic or necrotic brain tumours Magnetic resonance imaging Diffusion weighted images Apparent diffusion coefficient Magnetic resonance spectroscopy. Abbreviations: Ac : Acetate. ADC : Apparent Diffusion Coefficient. Cho : Choline. Cr : Creatine. DWI : Diffusion Weighted Imaging. MRS : Magnetic Resonance Spectroscopy. NAA : N-Acetyl Aspartate. TE : Echo Time. TR : Repetition Time. Correspondence to: Dr. Mohamed A. Hassaan, The Department of Radiodiagnosis, Faculty of Medicine, Cairo University Introduction THE evolution of a brain abscess is classically divided into four major stages: Early cerebritis, late cerebritis, early capsule formation, and late capsule formation. The capsular stage usually commences approximately at the end of the 2 nd week and can last several weeks to months [1]. Radiologically, a brain abscess in the capsule stage appears in CT and MR imaging as a rim-enhancing mass surrounded by edema, which is similar in appearance to necrotic malignant tumours, especially glioblastoma multiforme [2]. Intracranial cystic mass lesions represent a significant neurosurgical dilemma. Differentiation of various intracranial cystic lesions using CT and conventional MRI may sometimes be difficult because of nonspecific clinical findings and a similar appearance on imaging [3]. Using conventional CT and MR images to discriminate between the lesion types is often a very challenging task, and usually follow-up studies or biopsy procedures are required [4]. The medical management strategies for abscess and neoplasm are different. Correct diagnosis must be obtained before treatment of cystic brain lesions [5]. Knowledge of the exact nature of the lesion can help the neurosurgeon to determine the most appropriate management. For example, cerebral abscesses can be stereotactically aspirated, followed by intravenous antibiotic therapy, hence avoiding a formal craniotomy [6]. In vivo proton magnetic resonance spectroscopy (MRS) is a noninvasive technique to obtain the metabolite profile of normal and abnormal brain. 699

2 700 Role of MR Spectroscopy & Diffusion Weighted Techniques Several studies have suggested that MRS might noninvasively contribute to the establishment of the differential diagnosis between brain abscesses and cystic or necrotic brain tumours. The characterization of intracranial cystic lesions in these studies was based on the presence of specific metabolite resonances or a specific combination of known metabolites [7]. Diffusion-weighted imaging (DWI) provides a way to evaluate the diffusion properties of the water molecules in tissue and has been used in clinical applications such as ischemia, tumours, epilepsy, and white matter disorders [8]. DWI was said to be valuable in the differential diagnosis of abscesses and cystic or necrotic tumours [9]. In recent publications, DWI gave additional useful information in the differential diagnosis of intracranial cystic lesions [10]. Several publications have evaluated the role of either MRS or DWI separately, however the combination of both techniques for differentiation between brain abscesses and cystic or necrotic brain tumours is limited. The combination of MRS and DWI most probably will improve results compared with the use of only a single technique [10]. The aim of this study was to compare MRS findings and those of DWI with biopsy results to determine which technique is more effective in discriminating between abscesses, cystic and necrotic brain lesions. Patients and Methods Fifty patients (33 males & 17 females) having intracranial marginally enhancing cystic space occupying lesions on CT or conventional MRI, in which the differential diagnosis lies between brain abscesses versus cystic or necrotic tumours, were evaluated with DWI and MRS. Informed consent was obtained from the patients or from the nearest relative of the patients included in this study. Inclusion criteria: The presence of a cystic parenchymal lesion with variable perifocal edema and rim enhancement on post contrast study was the inclusion criterion for this study. Exclusion criteria: Those with ill-defined areas of signal alteration, patchy, partial, and incomplete areas of enhancement, as well as the absence of a well-formed cystic component were excluded. MR Technique : Magnetic resonance imaging were performed on a 1.5 T MRI system (Intera; Philips Medical Systems, Netherlands) or 1 T MRI system (Panorama; Philips Medical Systems, Netherlands) using a head coil. Total study time ranged from 45 to 60 minutes. Conventional MR : The routine imaging studies included T 1- weighted (TR/TE = 520/15ms), T2-weighted (TR/TE = 3900/100ms) and fluid-attenuated inversion recovery (FLAIR) (TR/TE = 6000/90ms; inversion time = 2000ms) sequences. Post contrast MRI was also performed in all patients after injecting gadolinium diethylenetriaminopentaacetic acid intravenously at a dose of 0.1mmol/kg body weight. Contraindications to IV contrast, as known hypersensitivity reaction or impaired renal functions were excluded first. Diffusion-weighted imaging : Diffusion-weighted echo-planar imaging in the axial plane was performed using the following parameters: TR/TE = 3000/95msec, number of excitations = 3. Diffusion-sensitizing gradients were applied along the 3 orthogonal directions with a diffusion sensitivity of b = 0 and 1000s/mm 2. Sections (5mm thick) with 2.5-mm intersection gaps, a 24-cm field of view, and a 128 x 256 matrix were used for all images. The signal intensity of the cystic or necrotic portion on diffusion-weighted images was defined by visual assessment as markedly low (signal intensity near that of CSF), slightly low (signal intensity between that of CSF and that of normal brain parenchyma), or slightly high, or markedly high compared with normal brain parenchyma. Analysis of diffusion changes was performed by the commercially available software for generation and analysis of apparent diffusion coefficient (ADC) maps. The ADC values were measured from ROIs manually drawn and placed in the most homogeneous area of the nonenhancing portion of the mass. MR spectroscopy : T1- and T2- weighted imaging were used for voxel localization. The selection of voxel position in the estimated center of the lesion was determined visually by examining the MR images in three orthogonal planes (sagittal, coronal, and axial) to define the volume of interest. A voxel of 1.5x1.5 x1.5cm to 2x2x2cm was used, depending on the

3 Mohamed A. Hassaan, et al. 701 size of lesion, was placed within the center of the cavity with the aim of avoiding contamination, if possible, from the surrounding brain parenchyma. Single voxel MRS was applied by using the method of point-resolved spectroscopy. After automated transmitter and receiver adjustment, the signal intensity over the volume of interest was automatically shimmed. Three spectroscopic sequences where taken in the center of the lesion: Short TE (TR/TE = 2000/36ms). Intermediate TE (TR/TE = 2000/144ms). Long TE (TR/TE = 2000/288ms). MR spectra were obtained with a TE of 144 to confirm the phase inversion associated with J- coupled metabolites of lactate, and amino acids, but not of lipids, which may be helpful to discriminate lactate or amino acid signals from lipid signals. In vivo spectroscopy data were analyzed using the commercially available processing software provided by Philips Medical Systems, Netherlands. Assignments of various resonances were based on the existing literature. The presence or absence of resonance peaks for choline, creatine, NAA, lipid, lactate, amino acids, succinate and acetate were recorded for each patient. In addition the Cho/Cr, Cho/NAA and NAA/Cr ratios were calculated. The peak areas of NAA, choline, and creatine were also measured in the corresponding contralateral normal-appearing brain tissue. Thus, each patient served as his or her own control. Diagnostic criteria: Final diagnosis: We divided the disease status into either an abscess or a tumour group according to the pathological, surgical and clinical data. Abscess : The diagnosis of brain abscess was made by pathology or stereotactic aspiration biopsy or on basis of clinical symptoms, laboratory data, and improvement in the follow-up imaging after antibiotic therapy. Tumour : All primary neoplasms were confirmed by surgery. The patient with metastatic tumour was diagnosed on the basis of clinical and radiological findings and had pathologically proven primary cancer. Diffusion-weighted images : The diagnosis of brain abscess was concluded when the cavity showed hyperintensity on DWI with ADC values less than 1x10 3 mm 2 /s, while the criteria for diagnosing tumour cysts were hypointensity on DWI with ADCs more than 1x10 3 mm 2 /s. MR spectroscopy : Diagnosis of abscess depends on the presence of amino acids with or without lactate, acetate and succinate, while tumour cysts depends on the presence of choline along with lactate or lactate only. On the basis of these criteria, the patients were categorized into one of two groups, an abscess group and a tumour group. In the absence of these criteria, the lesions were considered as inconclusive on the basis of diffusion imaging and MRS, respectively. Statistical analysis : Data were encoded and entered on an IBM compatible computer using computer programs Microsoft Excel version 12 (Microsoft Corporation, USA) and SPSS version 19 (Statistical Package for the Social Science; IBM Corporation, USA) statistical programs. Data were statistically described in terms of range, mean, standard deviation (±SD), frequencies (number of cases) and relative frequencies (percentages) when appropriate. Comparison between different groups in the present study was done using Student t-test for independent samples in comparing 2 groups of quantitative data when normally distributed and Mann Whitney U test for independent samples when not normally distributed. A probability value (p-value) less than 0.05 was considered statistically significant. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DWI and MRS with respect to final diagnosis for differentiation of cystic or necrotic tumour versus brain abscess were calculated to assess the efficacy of these modalities. They were calculated using a 2x2 contingency table displayed in (Table 1) (Chang et al., 2002). Results This study included 50 patients (33m & 17f). Their ages ranged from years with a mean of 44.8±18.4 (Mean±SD). Patients where distributed upon two groups namely the abscess group and the tumour group according to the final diagnosis. The abscess group included 18 patients (16 males and 2 females) while the tumour group

4 702 Role of MR Spectroscopy & Diffusion Weighted Techniques included 32 patients (17 males and 15 females). The patients in the abscess group had ages ranging from years with a mean of 49.0±19.5 while those in the tumour group had ages ranging from 1-66 years with a mean of 42.4±17.6. The most common diagnoses in the tumour group were glioblastoma multiforme followed by astrocytoma. The distribution of the patients in the tumour group is shown in (Table 2). Diffusion weighted images : The signal intensity of the cystic or necrotic portion on diffusion-weighted images was defined by visual assessment as markedly low, slightly low, slightly high, or markedly high. The results of the signal intensity in both groups are seen in (Table 3) and (Fig. 1). The results of the ADC values in both groups are seen in (Table 4). Significant difference was found between the ADC value in both groups ( p- value less than 0.01). The diagnosis of brain abscess was made in 15 patients out of 18 patients. The other 3 showed hypointense signal in DWI and ADC values above 1 (Figs. 2,3,4). Thirty one patients with necrotic or cystic tumours showed hypointense signal in DWI and ADC value above 1 (Figs. 5,6,7) with only one patient showing low signal in DWI. MR spectroscopy : According to the criteria of diagnosis of abscess and tumours, 14 patients out of the 18 patients in the abscess group was correctly diagnosed as brain abscess (Fig. 4). While 4 patients did not show MRS characteristics of brain abscess. Amino acids were detected in 14 patients in the abscess group, lactate in 14 patients, acetate in 6 patients and succinate in 6 patients. Lipids were detected in only one patient. Choline was detected in 5 patients, in whom 3 did not show amino acids, acetate or succinate and thus the diagnosis of abscess was not made while the other 2 showed amino acids and succinate and thus was diagnosed as abscess and the choline was considered as contamination from nearby tissues. The last patient that did not show MRS features of abscess did not show any MRS evidence of normal brain metabolites or evidence of amino acids, lactate, succinate or acetate. All patients showed absent or markedly reduced NAA and creatine compared to the normal appearing contralateral brain. Thirty patients out of 32 patients in the tumour group showed MRS characteristics of tumour (Fig. 7) while 2 patients showed MRS not diagnostic of tumours. Choline was detected in the 30 patients diagnosed as tumours, lactate in 12 patients and lipids in 7 patients. None of the patients showed amino acids, succinate or acetate. NAA and creatine were reduced or absent in all patients. In addition the Cho/Cr, Cho/NAA and NAA/Cr ratios were calculated. (Tables 5,6,7) shows comparison of these ratios between both groups. Statistically significant differences were found as regards the Cho/Cr, Cho/NAA ratios between both groups (p-values of 0.02 and 0.03 respectively), while no statistically significant difference was found as regards the NAA/Cr ratio. Sensitivity, specificity, positive predictive value and negative predictive value : Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DWI and MRS are shown in (Table 8) & (Fig. 8). Table (1): The 2x2 contingency table between the case number of the final diagnosis and the result according to the imaging modalities. Disease status according to imaging modalities Sensitivity = a/(a + c). Specificity = d/(b + d). PPV = a/(a + b). NPV = d/(c + d). Tumour (number) Infection (number) Final diagnosis Tumour (number) A C Infection (number) b d Total a+b c+d Total a+c b+d a+b+c+d Table (2): Distribution of the patients in the tumour group according to their final diagnosis. Glioblastoma multiforme 15 (47%) Astrocytoma 12 (38%) PNET 1 (3%) Spindle cell tumour (glial sarcoma) 1 (3%) Dysmoplastic infantile ganglioglioma 1 (3%) Ependymoma 1 (3%) Metastasis 1 (3%)

5 Mohamed A. Hassaan, et al. 703 Table (3): Signal intensity in DWI. Abscess Tumour Low 0 (0%) 15 (47%) Slightly low 3 (17%) 16 (50%) Slightly high 11 (61%) 1 (3%) Markedly high 4 (22%) 0 (0%) Table (8): Sensitivity, specificity, PPV, and NPV of DWI and MRS. DWI MRS Sensitivity 96.88% 93.75% Specificity 83.33% 77.78% PPV 91.18% 88.24% NPV 93.75% 87.5% Table (4): ADC values in both groups. Abscess Tumour Maximum Minimum Mean SD p-value <0.01 Table (5): Comparison Cho/Cr ratios in both groups. Abscess Tumour Maximum Minimum 0 0 Mean SD p-value Abscess Tumour Low Slightly Slightly Markedly low high high Fig. (1): Signal intensity in DWI. Table (6): Comparison Cho/NAA ratios in both groups. Abscess Tumour Maximum Minimum 0 0 Mean SD p-value 0.03 Fig. (2A) Fig. (2B) Table (7): Comparison NAA/Cr ratios in both groups. Abscess Tumour Maximum Minimum 0 0 Mean SD p-value 0.10 Fig. (2C) Fig. (2D)

6 704 Role of MR Spectroscopy & Diffusion Weighted Techniques Fig. (3A) Fig. (3B) Fig. (3C) Fig. (3D) Fig. (4A) Fig. (4B) Fig. (4C) Figs. (2,3,4): Male patient age 55 years with brain abscess secondary to left side otitis media. Axial T2 shows T2 hyperintense cystic lesion (Fig. 2a,b). Contrast enhanced MRI shows multiple left temporal ring enhancing lesions (Fig. 2c,d). DWI show restricted diffusion with ADC value of x 10-3 mm 2 /s at the larger anterior cavity and x 10-3 mm 2 /s at the smaller posterior cavity (Fig. 3a,b,c,d). MRS in short, long and intermediate TE was obtained from the largest anteriorly located cavity. It shows amino acid, acetate, succinate and lactate peaks. Note that both amino acids and lactate peaks inverted below base line at intermediate TE spectrums. Other normal brain metabolites as NAA and creatine are markedly reduced (Figs. 4 a,b,c). Fig. (5A) Fig. (5B) Fig. (5C) Fig. (5D)

7 Mohamed A. Hassaan, et al. 705 Fig. (5E) Fig. (5F) Fig. (6A) Fig. (6B) Fig. (7) Figs. (5,6,7): A case of pathologically proven glioblastoma multiformes in a female patient age 50 years complaining of headache and right side hemiparesis for several months. Axial T2 WIs showing left temporoparietal hyperintense T2 lesion (Fig. 5a,b). Her contrast enhanced MRI shows a marginally enhancing lesion at the left temporoparietal region with central breaking down (Fig. 5c,d,e,f). DWI show facilitated diffusion with ADC value of 1.275x10-3 mm 2 /s (Fig. 6a,b). Long TE MRS shows choline peak and small lipids/lactate peak. Markedly reduced NAA and creatine was also noted. Cho/Cr ratio is 2.9, Cho/NAA ratio is 3 and NAA/Cr ratio is 0.9 (Fig. 7) Sensitivity Specificity PPV NPV DWI MRS Fig. (8): Sensitivity, specificity, PPV, and NPV of DWI and MRS. Discussion Diagnosis of brain abscess is usually made on the basis of neuroimaging findings (e.g., CT and MR imaging findings) and clinical examination. Clinically, both brain abscesses and tumours may cause nonspecific headaches in the absence of fever, focal neurologic deficits, epileptic seizures, and disturbances in higher level cortical function. In addition, laboratory examination often shows normal white blood cell count. The neuroimaging appearance of some cystic or necrotic tumours are similar to that of brain abscesses [2,10]. The medical management strategies for abscess and neoplasm are different. Correct diagnosis must be obtained before treatment of cystic brain lesions [5]. Knowledge of the exact nature of the lesion can help the neurosurgeon to determine the most appropriate management. Neurosurgical biopsy, aspiration and drainage either stereotactic, ultrasound guided or free-hand is considered to be first-line treatment of cerebral abscesses, because expected brain tissue damage will be less compared to open surgery with abscess excision. Differentiation of brain abscesses from cystic or necrotic tumours is important not only in diagnosis and follow-up of antibiotic therapy but also will influence neurosurgical approach to these lesions. In case of an abscess, the centre should be target with intentions to aspirate pus and to culture the causing pathogens. In contrast, the optimal site for tissue diagnosis of a malignant cystic tumour is the contrast enhancing tumour rim [11] [12]. Diffusion-weighted imaging (DWI) provides a way to evaluate the diffusion properties of the water molecules in tissue and has been used in clinical applications such as ischemia, tumours, epilepsy, and white matter disorders [8]. DWI was said to be valuable in the differential diagnosis of abscesses and cystic or necrotic tumours [9]. In recent publications, DWI gave additional useful information in the differential diagnosis of intracranial cystic lesions [13].

8 706 Role of MR Spectroscopy & Diffusion Weighted Techniques In vivo magnetic resonance spectroscopy (MRS) is a noninvasive technique to obtain the metabolite profile of normal and abnormal brain. Several studies have suggested that MRS might noninvasively contribute to the establishment of the differential diagnosis between brain abscesses and cystic or necrotic brain tumours. The characterization of intracranial cystic lesions in these studies was based on the presence of specific metabolite resonances or a specific combination of known metabolites [7]. Application of DWI in distinguishing between brain abscesses and cystic or necrotic brain tumours has been reported to be useful in several publications. In the present study, 15 (83.3%) of 18 patients with brain abscesses showed hyperintensity on DWI and had ADC values less than 1x10-3 mm 2 /s in the range of to 0.912x10-3 mm 2 /s, whereas 3 patient with brain abscess presented with hypointensity on DWI and high ADC values above 1x10-3 mm 2 /s. One of these patients with facilitated diffusion was on antibiotic therapy before undergoing the MRI study. Conversely, 31 (96.9%) of 32 patients with cystic or necrotic tumours in the current study showed no restriction on DWI and had ADC values in the range of 1.1 to 3.156x10 3 mm 2 /s, whereas 1 tumour had hyperintensity on DWI and low ADC values (0.895x10 3 mm 2 /s). Overall DWI correctly classified the patients into either abscess or tumour in 46 (92%) patients out of 50. Significant difference was found between the ADC values of patients with brain abscess and necrotic or cystic tumour (p-value less than 0.01). In the current study most patients with brain abscess showed low ADC values while most patients with tumour showed higher ADC values. These results show that not all abscesses show reduced ADC values and not all cystic or necrotic neoplasms demonstrate increased ADC values. These results match with many previous studies where the ADC values of tumours were higher than those of abscesses. Noguchi et al., [14] reported ADC values of x 10-3 mm 2 /s in tumours and 0.7x 10-3 mm 2 /s in abscesses. Stadnik et al., [15] reported ADC values between 0.78x10-3 mm 2 /s and 1.79x10-3 mm 2 /s in tumours. In a study by Hakyemez et al., [16], 42 of 48 cases with the tumoural cavity the ADC values were 2.36±0.46x10-3 mm 2 /s. In the study done by NadalDesbarats et al., [17], the ADC values for abscesses were x10 3 mm 2 /s versus x10-3 mm 2 /s for cystic or necrotic tumours. Reddy and colleagues [18], found the ADC value of the abscess group to be 0.87± 0.05x10-3 mm 2 /s and was significantly low compared with the nonabscess group (2.89±0.05x10 3 mm 2 /s) (Reddy et al., 2006). Lai et al., found the ADC values of 20 out of the 21 cases with brain abscesses to be in the range of 0.41 to 0.87x10-3 mm 2 /s while the ADC values for 22 cases with cystic or necrotic tumours were in the range of 2.12 to 3.14x10-3 mm 2 /s, while one case of tumour showed low ADC value [10]. Also Reiche et al., [13] reported the ADC value of brain abscess in the range of x10-3 mm 2 /s while the tumours were in the range of 1.84 to 2.88x10-3 mm 2 /s [13]. The results of DWI in the current study were in good agreement with the findings of these previous studies. Previous studies used threshold ADC values for discrimination of brain abscess from cystic or necrotic tumours in the range of x10-3 mm 2 /s. In the current study, the threshold ADC value used was 1x10-3 mm 2 /s. The causes for restriction in pyogenic brain abscesses are microscopic organization of the tissues, high viscosity of pus resulting from high protein, and different types of viable or dead cells along with necrotic tissue and bacteria, which collectively impede the microscopic motion of water particles [19]. In contrast to abscesses the content of cysts and necrotic compartments of primary and secondary brain tumours consists of tissue debris and fewer inflammatory cells. Cyst fluid is almost clearer and more serous than pus. Hence, there are less diffusion barriers in tumour cysts than in abscess cavities [13]. Contrasting DWI studies of cystic or necrotic tumours still exist in the literature [10]. Park et al., [20] reported 2 cases of cystic or necrotic brain metastasis with markedly high signal intensity on DWI. Upon surgery, it was found that the cyst had a thick and creamy necrotic content similar to pus. Holtas et al., [21] reported a ring-enhanced brain metastasis with hyperintensity on DWI and a low ADC value in the necrotic part of the tumour. The reason for restricted diffusion was possibly early necrosis with intracellular edema of the lesion [21]. Chang et al., reported a ring-enhanced fibrillary low-grade astrocytoma with high signal intensity on DWI and a low ADC value, mimicking that of abscesses. Surgery revealed the presence of viscous creamy fluid within the tumour [9]. In a study by Reiche et al., two tumour cysts showed restricted diffusion with low ADC, and could not be differentiated precisely from abscesses. The histopathological findings of stereotactic biopsy and resection specimen revealed tumour coagulation necrosis in one case and large areas of necrosis in the other. Thus densely packed cell debris together with

9 Mohamed A. Hassaan, et al. 707 proteinaceous ingredients in tumour cysts may alter diffusion in a small number of patients [13]. Also there are cases of cerebral abscess cavities showing hypointensity on DWI and high ADC values which overlapped with findings of neoplastic cysts. Mishra et al. Reported, that pus culture from 5 out of 8 patients with high ADC was sterile and that an antibiotic drug therapy had been initiated already in these patients [22]. In the series of Reddy et al. 4 brain abscesses in 3 patients appeared isointense to hypointense on DWI and high ADC values were false negative and hence overlapped with those of tumour cysts [18]. Lai et al., described in 1 out of 21 patients with pyogenic abscesses hypointensity on DWI and high ADC. This patient had received antibiotic therapy for already 21 days. The cause of increasing diffusion in abscess cysts might be due to changes in pus composition and probably reflects increasing pus liquefaction as result of adequate antibiotic therapy [10]. Some investigators have suggested that variable concentrations of inflammatory cells and bacteria are present with different pathogenic organisms and that the host immune response and the age of an abscess might influence the viscosity of the pus, resulting in variations in ADC values [23]. Thus, using additional parameters, such as T2 hypointense rim characteristics, can increase confidence in differentiating these lesions. Although the T2 hypointense rim feature alone is not perfectly reliable in differentiating neoplasms from abscesses, the combination of this feature with ADC measurements allows separation of a subgroup of patients only with abscesses [4]. Based on the current study, restricted diffusion shown by ADC mapping is not pathognomonic for brain abscesses, because 16.7% of brain abscess lesions showed higher ADC, whereas 3.1% of lesions showed restricted diffusion among the tumour group and were inconsistent with the diagnosis. In most cases, diagnosis of a brain abscess can be made if the diffusion is restricted within a cystic ring-enhancing cerebral lesion with low ADC values and the diagnosis of tumour can be made if there is facilitated diffusion. MRS of the central cystic portion has been reported to allow the broad group of abscesses to be distinguished from tumours. The specific spectrum of the abscess cavity shows characteristic peak of amino acids with/without additional resonances of lactate, acetate and succinate, and this spectrum appears to be significantly different from the spectra of cystic or necrotic brain tumours [10]. Amino acids such as valine and leucine are known to be the end products of proteolysis by enzymes released by neutrophils in pus. Increases in lactate, acetate, and succinate presumably originate from the enhanced glycolysis and fermentation of the infecting microorganisms [24]. In MRS examination of the central cavity of cystic or necrotic brain tumours, an elevation in choline may be due to cell membrane synthesis, destruction, or both. Measurable levels of choline vary considerably, depending on the cellular attenuation, tumour grade, and presence or absence of necrosis. Paradoxically, some glioblastomamultiforme contain less choline than normal brain tissue, an effect of dilution of absolute cellular attenuation by the presence of extensive necrosis. In addition there is reduction of NAA and creatine in both brain abscesses and cystic or necrotic tumours than in the healthy brain tissue [25]. Most previous studies used single voxel MRS for special localization. A single voxel was placed in the central nonenhancing cystic part of the cavity. Only a few recent studies used multivoxel MRS and analyzed voxels from the central cystic part as well as the marginal enhancing wall. Analysis of the wall cannot be done with single voxel because the volume of the voxel is larger than in multivoxel and will include much contamination from the surrounding tissues. In this study single voxel technique was used and the voxel placed in the central part of the cavity. In our study, 14 (77.8%) out of the 18 patients with abscess cavities showed MRS specific for abscess while 4 patients having brain abscess did not show MRS findings of brain abscess. One of the patients with spectra not consistent with abscess was on antibiotic therapy before undergoing the MRS study. These brain abscesses were characterized by demonstration of amino acids with/without additional resonances of lactate, acetate, and succinate on MRS. Choline was observed in 2 patients with abscess probably due to the partial volume effect. Thirty (93.8%) patients out of 32 patients in the tumour group showed MRS characteristics of tumour while 2 patients showed MRS not diagnostic of tumours. Choline was elevated in the 30 patients diagnosed as tumours. None of the patients showed amino acids, succinate or acetate. NAA and creatine were reduced or absent in all patients in the abscess and tumour groups. MRS findings in this study are in agreement with previous studies [2,5,10,22,24]. MRS enabled a correct diagnosis of either brain abscess or cystic or necrotic tumour to be reached

10 708 Role of MR Spectroscopy & Diffusion Weighted Techniques in 44 (88%) patients out of the 50 patients included in this study. Absence of typical features of MR spectra from cases with abscesses, such as amino acid, acetate or succinate resonances may be due to infection with Staphylococcal aureus (facultative aerobic bacteria). Staphylococcal aureus is the cause of 10%-31% of cerebral abscesses. Thus, interpretation of in vivo MR spectra could allow us to distinguish between abscesses due to aerobic bacteria and those where anaerobic bacteria are present. However, the cystic components of the spectra in tumours and abscesses by aerobes microorganisms would be similar by demonstration of lipid and/or lactate [26]. Previous studies have reported that effective antibiotic treatment leads to the disappearance of amino acids, acetate and succinate but not lactate. Thus the spectra of treated abscess shows lactate alone and are similar to those of tumours. MR spectroscopic examinations should be performed as early as possible, preferably before the start of antibiotic therapy (Lai et al., 2002). Discrimination between amino acids (at 0.9 ppm) and lipid (at ppm) is important because lipid signals may exist in both brain tumours and abscesses, whereas amino acids are not seen in in vivo MRS of brain tumours. It is known that with a TE of 135 milliseconds, phase inversion occurs as a result of J-coupling between lactate and amino acid but not in lipid, a feature which may be helpful, along with the presence or absence of acetate or succinate, in differentiating brain abscess from tumour [27]. Lactate, which results from anaerobic glycolysis, can be detected in brain abscess as well as in cystic or necrotic brain tumours. Lipids indicate necrosis from cell membrane destruction and occur in both abscesses and cystic or necrotic tumours. In the present study, the lactate signal was found in 14 patients with brain abscess and 12 patients with cystic or necrotic tumours. On the other hand lipids were detected in one patient with brain abscess and 7 patients with cystic or necrotic tumours. The finding of a lactate peak and/or lipid peak in abscess and cystic or necrotic tumours is nonspecific and cannot be used to discriminate these two conditions without the presence of metabolites such as amino acids, acetate and succinate in abscesses and choline in tumours. It is not easy to differentiate lactate signals from lipid signals in clinical settings, and in many studies, lactate and lipid peaks were often combined and described as "lactate/lipid mixture". Both lactate and lipid signals are found in higher levels in high-grade tumours compared to low grade tumours [25,28,29]. There were significant differences between the Cho/Cr, Cho/NAA ratios between both groups (pvalues of 0.02 and 0.03 respectively), while no statistically significant difference was found as regards the NAA/Cr ratio. This can be attributed to the high levels of choline in brain tumours while choline should be typically reduced in patients with brain abscesses. Both brain tumours and abscesses show reduction of normal brain metabolites NAA and Cr. Thus it is expected that the Cho/Cr, Cho/NAA ratios would be higher in patients with tumours compared to abscesses. These results are in agreement with the previous study done by Lei et al. [2]. According to my knowledge all other previous studies did not compare the metabolite ratios, but they only used the presence of specific metabolite resonances or a specific combination of metabolites to either classify the patients as brain tumours or abscess. The combined DWI and MRS techniques have been used to separate between brain abscesses from cystic or necrotic tumours. Lai et al., found that the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DWI for differentiation of brain abscess from cystic or necrotic tumour were 95.2%, 95.7%, 95.2%, and 95.7%, whereas they were 85.7%, 100%, 100%, and 88.5% with MRS [10]. Mishra et al., have shown 72% sensitivity and 100% specificity for the differentiation of brain abscess from cystic or necrotic tumour on DWI and 96% and 100% on MRS, respectively [22]. However, Lai et al. have shown sensitivity and specificity of 95.2% and 95.7% for DWI and 85.7% and 100% for MRS, respectively [5]. In the current study, the sensitivity, specificity, PPV and NPV were 96.88%, 83.33%, 91.18% and 93.75% for DWI and 93.75%, 77.78%, 88.24% and 87.5% for MRS, respectively. DWI correctly classified the patients into either abscess or tumour in 46 (92%) patients which is slightly higher rate than MRS which correctly diagnosed 44 (88%) patients out of the 50 patients included in this study. Both DWI and MRS were able to reach the correct diagnosis better in the tumour group compared with the abcess group. The cause of abscesses having non-restricted diffusion may be due to pus liquification due to pervious antibiotic therapy. Also pathogenic organisms, host immune response and the age of an abscess might influence the

11 Mohamed A. Hassaan, et al. 709 viscosity of the pus. In this study data about previous antibiotic therapy was obtained from history taking and reviewing the patients charts. However history taking relies on the memory of the patients or their relatives which may suffer from imperfection. Also, unfortunately, the medical charts in our hospital are still manually done and there are no electronic charts. Searching through the patients charts manually is both time consuming and may be inaccurate. However to the best of my knowledge, three of the patients included in this study were receiving antibiotic therapy during the month preceding their MR examinations. In our study, with some exceptions, DWI and MRS provided a greater degree of confidence in distinguishing abscess from cystic or necrotic tumour than conventional MRI. In our study, conventional MRI, when combined with in vivo MRS and DWI, accurately predicted the diagnosis in 88% and 92% of the cases, respectively. Comparing DWI and in vivo MRS to differentiate brain abscess from necrotic brain tumour shows that DWI is more accurate in differentiating brain abscesses from cystic or necrotic tumours. DWI also requires less imaging time (about 40 seconds) compared to approximately five minutes for each of the MRS sequences (typically each patient needs 5 sequences). DWI is easier to interpret. Single-voxel MRS is more limited in voxel size from 1.5x1.5x1.5cm to 2x2x2cm than is DWI, and the smaller lesion viewed by MRS will be more affected by the partial volume effect. Although multivoxel imaging may have a smaller voxel than the single voxel technique in the case of small lesions, it is still more time consuming. If the lesion is located peripherally, spectrum of the lesion produced might be contaminated by the effect of neighboring fat. These findings are in agreement with previous studies [5,10,22]. Nevertheless, the combined use of MRS and DWI may improve results compared with the use of a single technique to differentiate brain abscess from cystic tumour. MRS and DWI complement conventional MRI for better characterization of intracranial cystic mass lesions. Further improvements can be done to better differentiate brain abscesses from cystic or necrotic tumours. First multivoxel MRS, which is becoming more available at clinical MRI equipment nowadays, may help better to reach a diagnosis. Although most previous studies using single voxel MRS placed this voxel at the center of the cystic lesion and did not include part of its wall, a more recent study by Lai et al., used multivoxel MRS and analyzed data from the wall of the lesion (Lai et al. 2008). Analysis of the wall of the lesion cannot be done with single voxel studies because the voxel size is larger than in the multivoxel technique and will include more of the adjacent structures than the wall of the lesion and metabolic data will be inaccurate. Voxels in the multivoxel technique are smaller and thus analysis of the wall of the lesions is more feasible. Also other MR techniques may be used for discriminating brain abscess from cystic or necrotic tumours, as diffusion tensor imaging (DTI) and perfusion weighted imaging as well as positron emission tomography-computed tomography (PET-CT) may be helpful. The use of these additional techniques will help to improve the accuracy of MR in differentiating brain abscesses from cystic or necrotic tumours. Conclusion : Comparing DWI and MRS to differentiate brain abscesses from cystic or necrotic brain tumours show that DWI is more accurate, requires less imaging time and is also easier to interpret. 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