Image findings of cranial nerve pathology on [18F]-2- deoxy-D-glucose (FDG) positron emission tomography with computerized tomography (PET/CT): a pictorial essay

Conventional CT and MRI have been the imaging modalities of choice for evaluation of cranial nerve (CN) pathology. However, CN pathology can also be detected on [18 F]-2- deoxy-D-glucose (FDG) positron emission tomography with computerized tomography (PET/CT) imaging [1‐3]. As FDG PET/CT is increasingly being used for oncologic imaging and more specifically for evaluation of head and neck (HN) cancer [4], PET/CT interpreters need to familiarize themselves with the image findings of CN involvement, which will greatly impact the staging and management of these patients.

Tumor related PET/CT findings include the perineural spread of HN tumors which represents a rare contiguous metastatic extension of tumor along a cranial nerve that portends to poor prognosis, even if the patient is asymptomatic [2, 5]. If present, treatment can be changed to include neck dissection, a larger radiation field, or adding adjuvant therapy [6‐8]. Facial nerve involvement (CN VII) in parotid tumors may preclude facial nerve–sparing surgery or require additional treatment modality [9]. Patients with skin cancer and perineural invasion will require adjuvant radiation therapy even when clear margins are achieved with Mohs surgery [10, 11]. Also the degree of FDG uptake by the tumor as measured by the SUV max is an important prognostic marker for locally advanced nasopharyngeal cancer. High FDG uptake reflects more aggressive tumors that may require more aggressive treatment and carries a worse prognosis, as compared to the less aggressive low FDG tumors [12].

Non-tumor related benign and malignant cranial nerve pathology can also be incidentally detected during PET/CT oncologic imaging including schwannomas [13], optic nerve glioma [14], meningioma [15], and melanoma [15]. Gallium 68 (68Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaceticacid (DOTA)–octreotate (DOTATATE, GaTate), has been shown to be more sensitive than FDG-PET/CT in detection of low grade somatostatin receptor positive tumors namely meningioma, esthesioneuroblastoma and schwannoma [16].

The purpose of this article is to describe the primary and secondary FDG-PET/CT findings of CN pathology and to provide a comprehensive illustration of the PET/CT cross-sectional anatomy and pathology of almost each individual CN, thus raising awareness and familiarity about incidental CN lesions seen on PET/CT, which will directly reflect on patient staging and management.

The primary sign of CN pathology includes linear thickening or linear increased/decreased FDG activity along the expected course of the CN (Fig. 1). For this purpose, all three planes (axial, coronal and sagittal) and maximum intensity projection (MIP) images must be evaluated and correlations with all other available imaging modalities, e.g. (CT or MRI) which will often confirm the abnormality.

The secondary signs of CN pathology include widening or destruction at the corresponding skull base foramen, asymmetric atrophy or abnormal activity in the muscles supplied by the CN, or increased FDG activity related to synergistic/antagonistic muscle overcompensation to maintain function (Table 1).

The main differential considerations for CN II lesion include optic pathway glioma (OPG), optic nerve sheath meningioma, idiopathic orbital inflammatory pseudotumor, and optic neuritis. FDG activity in Optic nerve glioma is variable depending on its histological grade [17, 18]. Some authors suggested the use of FDG-PET/CT in monitoring malignant transformation of OPG in children with neurofibromatosis type 1 syndrome [17, 19]. Optic meningioma is a benign tumor that typically demonstrate minimal to no FDG uptake on PET [15] and can be associated with bony sclerosis/destruction as in our case (Fig. 3). Orbital pseudotumor could be both hyper or isometabolic on FDG PET [18]. Xie et al. described a 56-year-old female with elevated FDG activity in several cranial and peripheral nerves suggestive of multiple neuritis, with patient“s symptoms improving following treatment [3].

Direct visualization of CNs III, IV and VI is usually beyond the resolution of PET/CT, however large brain stem or cavernous sinus lesions along the course of these nerves may indicate cranial nerve involvement by these lesions. Also, extraocular muscle atrophy or asymmetric decreased uptake could represent denervation injury, which should prompt a search for a lesion along the course of the innervating CN. In an attempt to compensate for the paralyzed muscle, the non affected extraocular muscles may show increased FDG activity, further confirming the CN involvement (Fig. 4c–e).

FDG-PET/CT can detect perineural tumor spread along the trigeminal nerve and its main divisions; most commonly arising from head and neck squamous cell carcinoma, adenoid cystic carcinoma, mucoepidermoid carcinoma, skin cancer and melanoma as well as [2] lymphoma [1] and neurolymphomatosis [20] (Fig. 5)

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The most common cerebellopontine angle lesions are vestibular schwannoma and meningioma. Vestibular schwannoma is typically described as a hypometabolic lesion [21], however in our experience they were hypermetabolic (Fig. 6c-f), which may be related to the large size of the lesions. Vestibular schwannoma is differentiated from meningioma by extension into the internal auditory canal (Fig. 6f). The less common facial nerve schwannoma is diagnosed when the lesion extends along the labyrinthine segment of CNVII (Fig. 6g, h). Perineural spread form parotid gland lesions should be suspected with abnormal activity extending superiorly along the stylomastoid foramen or within the temporal bone [2, 22, 23]. Rare CN melanoma metastasis along CNs VII and VIII has also been described [24].

The most common jugular foramen (JF) lesions that my involve CN X and XI are glomus juglare, schwannoma, meningioma and skull base metastasis. Looking at the bone margins of the JF on the bone window of PET/CT may help differentiate glomus tumors which tend to have a permeative destructive margins from schwannoma which tend to cause smooth expansion of the JF (Fig. 7e) and meningioma, which may have permeative sclerotic margins [25]. If the recurrent laryngeal branch of CNX is involved, it will be seen as a hypometabolic ipsilateral paralyzed vocal cord with a hypermetabolic overcompensating contralateral vocal cord (Fig. 7c, d). Ipsilateral shoulder dropping on MIP images (Fig. 7g), with atrophy of the trapezius and sternomastoid muscles on the axial images (Fig. 7c, d), signifies CNXI involvement, which could be secondary to CNXI sacrifice during neck dissection.

Injury of CNXII could occur by the aforementioned JF lesions [25]. Further distally it could be secondary to hypoglossal foramen lesions (CNXII Schwannoma [25, 26]), clival tumor (chordoma, chondrosarcoma and plasmacytoma) [25], or rarely could be secondary to retrospective perineural tumor spread from tongue base tumor or radiation injury. An atrophic sagging fatty infiltrated ipsilateral tongue will be seen with hypometabolism on PET/CT (Fig. 8 b, d, e) [25].

Cranial nerve pathology can be detected on FDG PET/CT. With the increased reliance on PET/CT in patient staging and follow-up, PET/CT interpreters should familiarize themselves with these findings as it may change patient staging and management.

“This retrospective study was approved by the Saint Louis University IRB board”.