Key words
aspergillosis - brain - mr imaging
Introduction
Candida ssp (subspecies), Aspergillus ssp and Cryptococcus ssp are the most common pathogens to cause fungal infections of the central nervous system (CNS) [1]. The source of infection is either a local process such as paranasal sinusitis, otogenic or odontogenic sources, or results from hematogenous spread, usually from the lung or the intestine [2]. A fungal infection of the CNS is rare in immunocompetent persons and is mostly observed in immunosuppressed patients, e. g. with AIDS or patients under medical immunosuppression after organ or bone marrow transplantation [3]. Another risk factor for acquiring cerebral fungal infections is long-standing diabetes.
The CNS manifestation is usually part of a disseminated infection [4]. Patients are often afebrile or only have a low-grade fever and present with nonspecific neurological symptoms such as stroke-like symptoms or seizures [5]. Cerebrospinal fluid (CSF) analysis typically shows a moderate elevation of CSF proteins and pleocytosis (600/mm), although CSF analysis can be normal as well. Blood cultures are frequently negative [6]. The nonspecific clinical presentation delays the diagnosis of a mycotic CNS infection and impairs the clinical outcome by a late initiation of effective treatment strategies. To increase knowledge of cerebral aspergilloma, we analyzed the imaging features of patients with this disease, which might facilitate earlier diagnosis in the future.
Case series
CT and MRI imaging data of nine patients with cerebral aspergillosis from two university hospitals were retrospectively analyzed in order to identify common imaging patterns. Diagnosis was confirmed by intraoperative biopsy by the neurosurgical department followed by histopathological analysis.
MR imaging examinations were performed on different MRI systems using 1.5- and 3-Tesla systems. The imaging protocols always included axial diffusion-weighted imaging (DWI), axial T2w images, axial and coronal T1w images and sagittal FLAIR images.
Results
Aspergillomas appeared as intra- or extra-axial mass lesions. The imaging findings in CT and MRI are summarized in [Table 1], [2].
Table 1
Description of CT findings in 8 patients with cerebral aspergilloma.
Tab. 1 Bildbefunde in der CT.
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CT features
|
n
|
(%)
|
|
Hypodense
|
3/8
|
38 %
|
|
Slightly hyperdense
|
4/8
|
50 %
|
|
Strongly hyperdense (hemorrhagic lesion)
|
1/8
|
13 %
|
Table 2
Description of MRI findings in 9 patients with cerebral aspergilloma.
Tab. 2 Beschreibung typischer Bildbefunde in der MRT.
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MRI sequence
|
MRI features
|
n
|
%
|
|
DWI
|
Strong diffusion restriction in the rim
|
9/9
|
100 %
|
|
ADC
|
Reduced ADC in the rim
|
9/9
|
100 %
|
|
T2w
|
Inhomogeneous abscess wall with onion-layer-like, strongly hypointense zones
|
9/9
|
100 %
|
|
T1w
|
Slightly hypointense
Moderately hypointense
Partly hyperintense
|
4/9
2/9
3/9
|
44 %
22 %
33 %
|
|
T1w+ Gadolinium
|
Strong enhancement in the rim
No enhancement
|
7/9
2/9
|
78 %
22 %
|
CT features
CT image datasets were available in 8 cases. Overall, CT did not demonstrate a characteristic appearance of the aspergillomas. The lesions were slightly hyperdense in 4 of 8 cases (50 %). In a single case the aspergilloma was strongly hyperdense due to hemorrhage (13 %). In 3 of 8 cases (38 %) the lesions were hypodense. In the majority of the cases, slight surrounding edema was observed.
MR imaging features
MR imaging datasets were available for all 9 patients. DWI showed rim-attenuated diffusion restriction in all patients (n = 9/9). Typical findings on T2w images were a hyperintense abscess wall, containing onion-layer-like hypointense zones, in particular on the inner part of the wall in 9/9 patients (100 %). After contrast media application, the majority (n = 7/9) of aspergillomas showed strong rim enhancement (78 %). ([Fig. 1]).
Fig. 1 Aspergilloma in the left frontal lobe with strong, rim-attenuated diffusion restriction, T2w-hyperintense abscess wall with a hypointense zone at the inner part of the wall. There is slight surrounding edema. No enhancement is seen after contrast media application.
Abb. 1 Aspergillom im linken Frontallappen mit starker wandständiger Diffusionsstörung. Die Abszesswand ist T2w-hyperintens und weist an der Innenseite hypointense Schichten auf. Es findet sich lediglich ein geringes perifokales Ödem. Nach Kontrastmittelapplikation last sich kein Enhancement beobachten.
Discussion
Patients with an intracranial manifestation of aspergillosis have a poor prognosis. Therefore, fast diagnosis is essential to initiate rapid, targeted medical and surgical treatment [7]. In our case series, we describe the typical imaging patterns of this rare cerebral infection to facilitate early diagnostic decision-making and improve the patients’ outcome ([Fig. 2]).
Fig. 2 There are multiple small aspergillomas with variable diffusion restriction and slight surrounding edema. The lesions show a hypointense center on T2w imaging and strong, rim-attenuated enhancement after contrast.
Abb. 2 Multiple kleine Aspergillome mit in Signalintensität variierender Diffusionsstörung und geringen perifokalen Ödemen. Zentral sind die Aspergillome hypointens in den Aufnahmen mit T2w-Bildbegebung. Nach Gadoliniumgabe läst sich ein kräftiges randständiges Enhancement abgrenzen.
Mycotic infections of the CNS are usually transmitted hematogenously. Lesions are therefore most commonly found in a subcortical location. Another means of infection is the transdural spread of an underlying paranasal sinus or mastoid infection [8].
In our study, all cerebral aspergillomas demonstrated pronounced diffusion restriction, in particular at the edge of the lesions. This finding is consistent with the fact that mycotic mass lesions have a peripheral fungal cell wall [9]. In contrast, intracerebral abscesses due to a bacterial infection are characterized by a strong diffusion restriction in the center of the abscess [10]. This diffusion restriction is caused by limited water diffusion as a result of the high cellularity of the pus. In T1w imaging, aspergillomas were mainly hypointense as a result of the cellular edema. T1w-hyperintense aspergillomas were seen in our study in three cases, most likely due to hemorrhage. After contrast media application, the majority of aspergillomas (78 %) showed strong enhancement in the rim. However, in two cases no enhancement was seen at all. This observation was already made in prior studies, suggesting that strongly immunosuppressed patients are not able to induce a sufficient inflammatory response at the blood-brain barrier to allow passage of the contrast agent [11]. The observation that aspergillomas are characterized by diverging hypointense layers in T2-weighted images was also made before [12]. The T2-hypointensities correlate with the grade of fungal proliferation. Since it is essential for fungal growth, the hyphae accumulate iron and magnesium, leading to a paramagnetic effect. It can be assumed that the strongly hypointense layers correlate with areas of active proliferation in the interior part of the abscess wall where the fungal proliferation encounters less host immune defense [13].
Differential diagnoses of ring enhancing intracranial mass tumors include metastases, primary or secondary brain tumors and abscesses caused by different types of infection. Anamnesis, as well as further extracranial examination with ultrasound, X-ray or CT helps to identify metastases. Typical image patterns have been described for various intracranial infections, which help to discriminate between the types of infection. Differential diagnoses for the cases examined in this study are bacterial abscesses, which are characterized by a typical general diffusion restriction, as well as tuberculomas or toxoplasmosis [14]. Cerebral blood volume maps obtained by CT and MR perfusion are useful to identify primary brain tumors or lymphomas. The latter is characterized by the typical leakage in MR perfusion due to higher vascular permeability [15].
In summary, our case series demonstrates typical MR imaging, while CT features were less typical. There was generally a strong diffusion restriction in the rim. On T2-weighted images the abscess wall was typically hyperintense with onion-layer-like hypointense zones, which were particularly prominent at the innermost part of the abscess wall. Rim enhancement was seen in the majority of the cases. However, these findings can vary, e. g. due to the immuno-status of the patient.
Cerebral aspergillosis is an often fatal complication with a subtle clinical presentation. The aim of this study was to describe typical imaging findings of cerebral aspergillomas in order to facilitate early diagnosis and initiate rapid and effective antifungal treatment.
