Brain metastases: neuroimaging

Abstract

Magnetic resonance imaging (MRI) is the cornerstone for evaluating patients with brain masses such as primary and metastatic tumors. Important challenges in effectively detecting and diagnosing brain metastases and in accurately characterizing their subsequent response to treatment remain. These difficulties include discriminating metastases from potential mimics such as primary brain tumors and infection, detecting small metastases, and differentiating treatment response from tumor recurrence and progression. Optimal patient management could be benefited by improved and well-validated prognostic and predictive imaging markers, as well as early response markers to identify successful treatment prior to changes in tumor size. To address these fundamental needs, newer MRI techniques including diffusion and perfusion imaging, MR spectroscopy, and positron emission tomography (PET) tracers beyond traditionally used 18-fluorodeoxyglucose are the subject of extensive ongoing investigations, with several promising avenues of added value already identified. These newer techniques provide a wealth of physiologic and metabolic information that may supplement standard MR evaluation, by providing the ability to monitor and characterize cellularity, angiogenesis, perfusion, pH, hypoxia, metabolite concentrations, and other critical features of malignancy. This chapter reviews standard and advanced imaging of brain metastases provided by computed tomography, MRI, and amino acid PET, focusing on potential biomarkers that can serve as problem-solving tools in the clinical management of patients with brain metastases.

Keywords: MRI; PET; amino acid; brain; diffusion; imaging; metastasis; perfusion.

Fig. 7.1.

Noncontrast computed tomography (CT) has low sensitivity for brain metastases. A noncontrast CT image (A) through the posterior fossa is essentially unremarkable. T2-weighted image (B) of the same patient shows extensive abnormality of the cerebellum, with a very large number of metastases most clearly defined by postcontrast T1-weighted images (C).

Fig. 7.2.

Abnormally restricted diffusion is a typical finding for cerebral abscess, but may occasionally occur in brain metastases. Each column represents a different patient. (A–C) Diffusion-weighted images; (D–F) postcontrast T1-weighted images. Abscess (A, D), mucinous colon metastasis (B, E), epidermoid (C, F). Note lack of enhancement at the margins of the epidermoid, unlike the other two lesions (F, arrows).

Fig. 7.3.

A wide variety of pathologies can generate a single ring-enhancing parenchymal brain lesion that resembles metastatic disease. Postcontrast T1-weighted images of the brain demonstrating (A) toxoplasmosis, (B) neurocysticercosis, (C) glioblastoma, (D) tumefactive multiple sclerosis, (E) lymphoma in an immunocompromised patient, and (F) lung carcinoma metastasis. Note incomplete ring enhancement (arrow) with some internal enhancement (arrowhead) in the patient with multiple sclerosis (D). This finding is suggestive of demyelinating disease.

Fig. 7.4.

Perfusion imaging can help distinguish metastases from some, but not all, potential mimics. T1-weighted (A), T2-weighted (B), postcontrast T1-weighted (C), and cerebral blood volume map from dynamic susceptibility contrast perfusion images (D) of the posterior fossa with region of interest (circles) are displayed. A heterogeneously enhancing lesion in the region of the right lateral aperture of the fourth ventricle (circles) is nonspecific in appearance. However, very low relative cerebral blood volume (D) of 0.27 of the mass indicated a lower likelihood of metastatic disease. Neurosurgical resection followed by histopathologic analysis resulted in the diagnosis of cavernous malformation.

Fig. 7.5.

Potential of advanced imaging to generate early response markers after treatment. Two patients with breast brain metastases received stereotactic radiosurgery and subsequently magnetic resonance imaging with perfusion imaging 1 month later. In the first patient (A, B), a nonresponder, two enhancing lesions on the postcontrast T1-weighted image (A, arrows) show elevated relative cerebral blood volume (rCBV) above 3.0 (B). Conversely, the second patient has a ring-enhancing lesion of similar size (C, arrow), which shows low rCBV (< 1). Three-month follow-up images (E, F) show interval growth of one of the metastases with high rCBV (E, arrow). The second metastasis for this patient was resected due to increasing mass effect. Conversely, the metastasis from the responder (F, arrow), shows no interval growth compatible with a sustained response.

Fig. 7.6.

Perfusion imaging can help distinguish true from pseudoprogression. This patient with a history of brain metastases treated with radiation therapy developed a new ring-enhancing lesion on postcontrast T1-weighted images (A) adjacent to the right lateral ventricle. Low relative cerebral blood volume (B) was compatible with treatment effect rather than tumor recurrence and this was confirmed on biopsy (C). The patient subsequently underwent magnetic resonance imaging-guided laser ablation of this lesion with improved symptomatology.

Fig. 7.7.

Potential added value of positron emission tomography (PET) imaging to help diagnosis radiation necrosis. Postcontrast T1-weighted images depict a left frontal-lobe lung carcinoma metastasis (arrows). The small lesion at baseline (time of stereotactic radiosurgery, A) appears to diminish slightly in size by 4 months posttreatment (B). However, the lesion is much larger in the follow-up scan 2 months later (C), but 18-fluorodeoxyglucose (FDG) PET (D) at that time demonstrated little tracer uptake, consistent with radiation necrosis rather than tumor progression. Subsequent imaging (E) shows the lesion (without additional treatment) beginning to regress, compatible with radiation necrosis.

Fig. 7.8.

Time–activity curves may add value to static O-(2-[¹⁸F]fluoroethyl)-l-tyrosine (FET)-positron emission tomography (PET) images for the identification of metastases versus treatment effect. Radiation injury mimicking tumor recurrence (C) exhibits increasing FET uptake (A), whereas recurrent tumor (D) shows an increase followed by a decline in FET uptake (B). NSCLC, nonsmall cell lung cancer; ROI, region of interest; SUV, standardized uptake value. (Reproduced from Galldiks N, Langen KJ, Pope WB (2015) From the clinician’s point of view – what is the status quo of positron emission tomography in patients with brain tumors? Neuro Oncol 17: 1434–1444, with permission from Oxford University Press.)

Fig. 7.9.

Potential advantage of amino acid positron emission tomography (PET) in identifying tumor recurrence. A patient with a history of successfully treated thyroid brain metastasis with a remnant punctate focus of enhancement present on postcontrast T1-weighted images (A, arrow) in the right central sulcus region. This lesion did not show tracer uptake on 18-fluorodeoxyglucose (FDG) PET (B, arrow), but high cortical background activity, as typically seen in FDG PET, reduces sensitivity for small lesions. One year later the patient developed increased enhancement in the region (C, arrow), which was thought to represent either recurrence or a radiation-induced cavernous malformation. 3,4-Dihydroxy-6-[¹⁸F]-fluoro-l-phenylalanine (FDOPA) PET (D, arrow) showed the lesion to have high tracer uptake, compatible with recurrence, which was subsequently confirmed at surgery. Note the reduced background cortical activity of FDOPA PET (D) compared to FDG PET (B).

Fig. 7.10.

Effects of bevacizumab treatment on radiation necrosis. A patient with a cerebral testicular metastasis visible as a ringenhancing lesion on postcontrast T1-weighted images (A) was treated with resection (B) followed by radiation therapy. Subsequently the patient became symptomatic and follow-up imaging showed increased enhancement around the resection cavity (C). This was thought to represent radiation necrosis and the patient was treated with bevacizumab with reduction in enhancement (D) and reduced symptomatology. However the patient’s symptoms returned and he was found to have a diffusion-restricted lesion around the resection cavity (E), which was confirmed to be radiation necrosis after a second surgery. The development of persistent diffusion-restricted lesions associated with radiation necrosis also has been described in patients with high-grade glioma treated with chemoradiation therapy followed by bevacizumab.