**5. Differential diagnosis**

#### **5.1. Tumefactive demyelinating lesions**

Tumefactive demyelinating lesions (TDLs) can be seen either during a relapse of a known multiple sclerosis or on acute onset. TDL can mimic high‐grade gliomas on conventional MRI. In both conditions, there is contrast enhancement, perilesional edema, and central necrosis. Additional histopathology is not always straightforward since abnormal mitotic figures in reactive astrocytes can be present. In TDL, there is usually incomplete rim enhancement on MRI and little mass effect and edema (**Figure 6**).

**Figure 6.** A case of TDL demonstarting incomplete rim enhancement on sagittal T1-weighted images after intravenous contrast administration.

#### *5.1.1 Diffusion‐weighted imaging*

Min ADC values were higher in TDL than in PCNSLs or high‐grade gliomas given that TDL is lesser cellular lesions than both PCNSLs and high‐grade gliomas [18]. An important exception might be an acute demyelinating lesion which has areas of low ADC values (**Figure  7**). In acute phase in the TDL rim, there is peripheral restricted diffusion. The abnormal

diffusion resolves within 1–3 weeks. Following restricted diffusion on initial MRI, subse‐ quent Gd enhancement can be seen [19].

**Figure 7.** A case of TDL (A) demonstrating moderate ADC values (B). The rCBV maps show no elevation of Blood volume compared with contralateral normal white matter (C).

#### *5.1.2. Perfusion imaging*

**4.3. MR spectroscopy**

172 Neurooncology - Newer Developments

**5. Differential diagnosis**

contrast administration.

*5.1.1 Diffusion‐weighted imaging*

**5.1. Tumefactive demyelinating lesions**

MRI and little mass effect and edema (**Figure 6**).

Characteristic spectroscopic findings for PCNSL include elevated signals of lipid, choline, and lactate and reduced NAA signal **(Figure 5**). Large lipid peaks on lesions without central necrosis are also strongly suggestive of PCNSL [17]. High lipid peak may be due to in‐

Tumefactive demyelinating lesions (TDLs) can be seen either during a relapse of a known multiple sclerosis or on acute onset. TDL can mimic high‐grade gliomas on conventional MRI. In both conditions, there is contrast enhancement, perilesional edema, and central necrosis. Additional histopathology is not always straightforward since abnormal mitotic figures in reactive astrocytes can be present. In TDL, there is usually incomplete rim enhancement on

**Figure 6.** A case of TDL demonstarting incomplete rim enhancement on sagittal T1-weighted images after intravenous

Min ADC values were higher in TDL than in PCNSLs or high‐grade gliomas given that TDL is lesser cellular lesions than both PCNSLs and high‐grade gliomas [18]. An important exception might be an acute demyelinating lesion which has areas of low ADC values (**Figure  7**). In acute phase in the TDL rim, there is peripheral restricted diffusion. The abnormal

creased turnover of the membrane components in transformed lymphoid cells.

TDL shows significant lower rCBV values (mean 0.88 ± 0.46) than high‐grade gliomas (mean 6.47 ± 6.52), given the increased angiogenesis that the latter have (**Figure 7**). However, PCNSL had a less pronounced difference with a mean value of 2.11 ± 0.53 [20].

#### *5.1.3. MR spectroscopy*

TDL findings on spectroscopy are usually involve an elevated choline peak and reduced NAA signal. There may be also increased lactate and increased Cho/NAA that can reach high levels similar to that of high‐grade gliomas; thus, differential diagnosis is problematic. The detec‐ tion of glutamate and glutamine elevations has also been suggestive of TDL [21].

#### **5.2. Brain abscess**

Brain abscesses usually result from the extension of inflammation from the sinuses, the orbit, the mastoid cells, or the middle ear. As possible ways of spreading are either direct infection from a penetrating trauma, septic emboli, and contiguous or hematogenous spread. The most common pathogen is *Streptococcus pneumoniae*. Symptomatology is similar to any other mass lesions but tend to progress rapidly. Classical MRI findings of abscess in T2‐weighted images are high‐signal intensity with a thin rim of low intensity surrounded by edema. Further‐ more, satellite lesions are more common in abscesses contrary to neoplastic lesions.

#### *5.2.1. Diffusion‐weighted imaging*

The characteristic finding of brain abscess in DWI is a core of restricted diffusion due to pus consistency, whereas in neoplasms, there is usually low DWI signal (**Figure 8**). However, some necrotic brain metastasis may also display high signal intensity on DWI [22]. ADC values usually increase as treatment is successful even if cavity remains. Another finding in the rim of neoplastic lesions is a lower ADC value than that of an abscess.

**Figure 8.** A case of an abscess (A) revealing low ADC values corresponding to the nonenhancing portion of the abscess (B).

## *5.2.2. Perfusion imaging*

Contrary to glioblastomas and metastases, the enhancing rims of abscesses usually demon‐ strate lower rCBV values. The rCBV ratio of the enhancing portions of abscesses has be reported to be 0.79 ± 0.18, whereas in tumors was 1.40 ± 0.54 [23].

## *5.2.3. MR spectroscopy*

Relative‐specific MR spectroscopic feature of brain abscess is a succinate peak; however, it is not present in all cases. Apart from that elevated peaks of lactate, acetate, amino acids, alanine, valine, leucine, and isoleucine can be found. In abscesses reduced peaks of Cho/Crn and NAA are usually present [24]. Tuberculous abscesses typically have high lipid (mostly short‐chain fatty acids such as butyric, isobutyric, caproic). Disappearance of metabolites of bacterial origin has been correlated with positive response to therapy [25].

#### **5.3. Encephalitis**

Encephalitis is an acute, usually diffuse, inflammatory process affecting the brain and may mimic mass lesions. Herpes simplex (HSV) encephalitis is the most common cause. Biopsy is helpful in some instances. Patients are usually confused and disoriented at the beginning and progress to coma within days. MRI demonstrates edema as high signal on T2, primarily within the temporal lobe, that may extend across sylvian fissure. Enhancement is usually present after the second week. Foci of hemorrhage occasionally can be found on MRI.

## *5.3.1. Diffusion‐weighted imaging*

Encephalitis typically demonstrates low ADC values due to cytotoxic edema. However, encephalitis may mimic an infarct that involves the cortical regions of the temporal lobe.

#### *5.3.2. Perfusion imaging*

usually increase as treatment is successful even if cavity remains. Another finding in the rim

**Figure 8.** A case of an abscess (A) revealing low ADC values corresponding to the nonenhancing portion of the abscess

Contrary to glioblastomas and metastases, the enhancing rims of abscesses usually demon‐ strate lower rCBV values. The rCBV ratio of the enhancing portions of abscesses has be reported

Relative‐specific MR spectroscopic feature of brain abscess is a succinate peak; however, it is not present in all cases. Apart from that elevated peaks of lactate, acetate, amino acids, alanine, valine, leucine, and isoleucine can be found. In abscesses reduced peaks of Cho/Crn and NAA are usually present [24]. Tuberculous abscesses typically have high lipid (mostly short‐chain fatty acids such as butyric, isobutyric, caproic). Disappearance of metabolites of bacterial origin

Encephalitis is an acute, usually diffuse, inflammatory process affecting the brain and may mimic mass lesions. Herpes simplex (HSV) encephalitis is the most common cause. Biopsy is helpful in some instances. Patients are usually confused and disoriented at the beginning and progress to coma within days. MRI demonstrates edema as high signal on T2, primarily within the temporal lobe, that may extend across sylvian fissure. Enhancement is usually present after

of neoplastic lesions is a lower ADC value than that of an abscess.

(B).

*5.2.2. Perfusion imaging*

174 Neurooncology - Newer Developments

*5.2.3. MR spectroscopy*

**5.3. Encephalitis**

to be 0.79 ± 0.18, whereas in tumors was 1.40 ± 0.54 [23].

has been correlated with positive response to therapy [25].

the second week. Foci of hemorrhage occasionally can be found on MRI.

Perfusion MRI has not been widely studied in encephalitis. At an early stage, there is an abnormal increase of blood flow in the affected area, followed by hypoperfusion at a later stage.

#### *5.3.3. MR spectroscopy*

On MR spectroscopy, finding encephalitis needs to be differentiated from a low‐grade glioma which has similarfindings. In general, there is a decrease in NAA peak usually 1–2 weeks after onset. After clinical recovery, there is a corresponding increase in NAA [26, 27]. Frequently, there is an increase in choline and myoinositol peak. An increased Cho/Cr ratio may be attributed to myelin breakdown. Sporadically, the lactate peak may be elevated.

#### **5.4. Metastasis**

Although the annual incidence of brain tumors is 17,000, for brain metastasis is 170,000 [28]. Thus, brain metastasis is the most common brain tumor seen clinically. The source of more than 50% of metastatic lesions is lung and breast cancer. When a single‐brain lesion is found in a patient with a history of cancer, in 11% of these cases the lesion will not be metastatic. Four out of five of solitary metastases are located in the cerebral hemispheres. The majority tends to occur atthe gray/white matterjunction and is usually located posteriorto the Sylvian fissure.

#### *5.4.1. Diffusion‐weighted imaging*

The characteristic diffusion‐weighted imaging feature for metastatic neoplasms is an elevat‐ ed ADC. However, there is an overlap of the ADC values of metastatic lesions with those of primary neoplasms (**Figure 9**). Evaluation of ADC values in the non‐enhancing T2‐hyperin‐ tense areas surrounding the lesion may provide clues for the differentiation of high‐grade gliomas from metastasis, given the lower ADC values in infiltrated areas of primary neo‐ plasms compared with metastatic lesions. A threshold value of 1.302 × 10-3 mm<sup>2</sup> /s for the minimum ADC value in the peritumoral regions had a sensitivity of 82.9% and specificity of 78.9% for distinguishing between glioblastoma and metastasis [29]. Although some studies have not found correlation between restricted diffusion or ADC values and various histolog‐ ic types of metastases; however, a study reported that well‐differentiated adenocarcinomas had lower DWI signal intensity compared with poorly differentiated carcinomas [30, 31].

**Figure 9.** There is overlapping in the ADC values between a metastatic (A) and a primary brain tumor (B).

#### *5.4.2. Perfusion imaging*

Angiogenesis is essential for metastatic tumors growth. Thus, these lesions are associated with increased rCBV values compared with contralateral normal white matter. Thus, perfusion metrics tend to overlap between high‐grade gliomas and metastatic lesions (**Figure 10**). The peak height and the percentage of signal intensity recovery derived from the T2\* relaxivity curve on DSC MR has been reported to provide important clues [32]. Apart from that, metastasis from melanoma and renal cell carcinoma has been reported to have significant higher rCBV values than high‐grade gliomas and metastases from lung cancer [33].

**Figure 10.** Both glioblastoma (A, B) and metastatic lesions (C, D) exhibits increased rCBV values, not permitting a dif‐ ferentiation based on perfusion imaging.

The rCBV values of perilesional area are usually higher for gliomas than metastatic lesions, due to glioma's infiltrative nature. In a study of 22 high‐grade gliomas and 26 metastatic lesions, the rCBV ratios of peritumoural edema were 0.89 ± 0.51 in high‐grade gliomas and 0.31 ± 0.12 in metastasis. A threshold rCBV value of 0.46 has been proposed, with a sensitivi‐ ty of 77.3% and specificity of 96.2% for the differentiation of the two entities [34].

#### *5.4.3. MR spectroscopy*

**Figure 9.** There is overlapping in the ADC values between a metastatic (A) and a primary brain tumor (B).

higher rCBV values than high‐grade gliomas and metastases from lung cancer [33].

Angiogenesis is essential for metastatic tumors growth. Thus, these lesions are associated with increased rCBV values compared with contralateral normal white matter. Thus, perfusion metrics tend to overlap between high‐grade gliomas and metastatic lesions (**Figure 10**). The peak height and the percentage of signal intensity recovery derived from the T2\* relaxivity curve on DSC MR has been reported to provide important clues [32]. Apart from that, metastasis from melanoma and renal cell carcinoma has been reported to have significant

**Figure 10.** Both glioblastoma (A, B) and metastatic lesions (C, D) exhibits increased rCBV values, not permitting a dif‐

*5.4.2. Perfusion imaging*

176 Neurooncology - Newer Developments

ferentiation based on perfusion imaging.

Accurate differentiation between high‐grade gliomas and metastatic lesion based on the enhancing part is problematic based on MR spectra. In metastatic lesions, there is no NAA peak, whereas necrosis results in a lipid peak. Lipid and lactate may be also elevated in primary brain tumors due to necrosis. Myoinosital peaks have not been reported to date in brain metastases, contrary to high‐grade gliomas which tend to have elevated peaks [35, 36]. Given that primary tumors have a tendency to infiltrate, evaluation of the T2 hyperintense perile‐ sional tissue provide more important information. Thus, although there is an intratumoral choline peak in both primary and metastatic lesions, there is no choline elevation in the peritumoural edema in metastatic lesions [37].
