Clinical PET/MRI in neurooncology: opportunities and challenges from a single-institution perspective

Abstract

Purpose: Magnetic resonance imaging (MRI) plays a key role in neurooncology, i.e., for diagnosis, treatment evaluation and detection of recurrence. However, standard MRI cannot always separate malignant tissue from other pathologies or treatment-induced changes. Advanced MRI techniques such as diffusion-weighted imaging, perfusion imaging and spectroscopy show promising results in discriminating malignant from benign lesions. Further, supplemental imaging with amino acid positron emission tomography (PET) has been shown to increase accuracy significantly and is used routinely at an increasing number of sites. Several centers are now implementing hybrid PET/MRI systems allowing for multiparametric imaging, combining conventional MRI with advanced MRI and amino acid PET imaging. Neurooncology is an obvious focus area for PET/MR imaging.

Methods: Based on the literature and our experience from more than 300 PET/MRI examinations of brain tumors with ¹⁸F-fluoro-ethyl-tyrosine, the clinical use of PET/MRI in adult and pediatric neurooncology is critically reviewed.

Results: Although the results are increasingly promising, the added value and range of indications for multiparametric imaging with PET/MRI are yet to be established. Robust solutions to overcome the number of issues when using a PET/MRI scanner are being developed, which is promising for a more routine use in the future.

Conclusions: In a clinical setting, a PET/MRI scan may increase accuracy in discriminating recurrence from treatment changes, although sequential same-day imaging on separate systems will often constitute a reliable and cost-effective alternative. Pediatric patients who require general anesthesia will benefit the most from simultaneous PET and MR imaging.

Keywords: 18F-fluoro-ethyl-tyrosine; Brain tumor; FET; Glioma; Multiparametric imaging; PET/MRI; Pediatric.

Fig. 1

Multimodality tumor characterization. A combined 40 min dynamic FET PET/MRI with DSC BV and single voxel MRS was performed in a 7-year-old boy with an incidentally found lesion in the right basal ganglia area. Post-contrast T1 (CE T1) and T2 FLAIR show a solitary contrast-enhancing lesion without edema. Supplementary imaging included: DWI showing high ADC and thus not indicative of increased cellularity; MRS (short echo time) demonstrating only moderately increased choline (Cho/NAA = 1.36 and Cho/Cr = 1.23); leakage-corrected DSC BV did not show increased BV; dynamic FET PET scanning found moderately increased uptake (T _max/B = 2.1) with an increasing time–activity curve. Based on the combined imaging, a differentiation of a neoplasm from inflammatory (or other non-neoplastic) pathology could not be made, but it was concluded that a high-grade glioma or other aggressive malignancy was unlikely. Follow-up MRI after 3 months showed regression of contrast enhancement pointing toward a demyelinating lesion

Fig. 2

Multiparametric PET/MRI imaging. Transaxial images of glioblastoma (WHO IV) patient 2–3 weeks after surgery showing post-contrast MRI (CE T1), FET PET and FDG PET (top row), and blood volume (BV) and permeability (Ki) maps derived from dynamic contrast-enhanced (DCE) T1 MRI scans [48]. DCE allows for the separation of contrast enhancement in a blood volume (BV) and permeability (Ki) component. The physiological measures highlight different and complementary tumor characteristics. FET PET shows a superior contrast to healthy brain in delineating the tumor borders, and peak areas (yellow arrow) are not overlapping in metabolic and vascular physiological measures. FDG PET is challenged by high uptake in functioning neural tissue

Fig. 3

Presurgical planning. Sagittal images of a 15-year-old boy with pilocytic astrocytoma (WHO I). Post-contrast T1 MRI (upper left) showed contrast-enhancing tumor (red arrow) with high metabolic activity on FET PET in the anterior parts of the tumor (T _max/B = 2.7, biological tumor volume = 2 ml). Tractography from diffusion tensor imaging coregistered to pre-contrast T1 MRI (lower left) showed a close relationship of the corticospinal tract (blue arrow) to the tumor (red arrow). Thus, chemotherapy was decided to be safer than surgery

Fig. 4

Tumor recurrence vs. treatment effects. Transaxial T1-weighted post-contrast MRI (top row CE T1), FET PET (center row) and leakage-corrected blood volume maps (bottom row DSC BV) in a patient with deep-seated glioblastoma multiforme (WHO IV) in the left inferior occipito-temporal lobe. The initial scans at radiotherapy planning (left) show 6 cm³ of metabolically active tumor with FET uptake (red arrow, T _max/B = 2.7). Six months after termination of adjuvant temozolomide (TMZ), CE T1 MRI found increased contrast enhancement in the left hippocampus suspicious of tumor recurrence, and the patient was scheduled for second-line chemotherapy. However, recurrence could not be corroborated by supplementary FET PET/MRI DSC scanning (cyan arrow, T _max/B = 1.4). Evidence of tumor angiogenesis could not be identified with certainty because of the high blood volume signal from surrounding vasculature and choroid plexus. Follow-up FET PET/MRI DSC after 3 months untreated showed stable conditions (right column) supporting treatment effects

Fig. 5

Limitations of multimodal imaging. Transaxial slices of contrast-enhanced T1 (CE T1), FET PET and DSC BV imaging, compromised by imaging artifacts. The patient in the upper row had prior surgery and radiotherapy for a sinonasal carcinoma and was referred to distinguish tumor recurrence from treatment effects. FET PET showed increased activity in the border of the lesions in the frontal region (T _max/B = 3.2) indicating recurrence, whereas blood volume imaging (DSC BV) was not useful due to a severe susceptibility artifact induced by the inserted titanium net. The bottom row shows a patient with recurrent glioblastoma (WHO IV). Excellent agreement of blood volume imaging (DSC BV) and FET activity distribution is demonstrated, but CE T1 image quality is degraded due to pronounced patient motion. Often a 2D T1 sequence less sensitive to patient motion must be added

Fig. 6

PET/MRI attenuation correction. Sagittal and axial image of simultaneous 18F-FET PET/MRI acquisition of a 55-year-old female with anaplastic oligodendroglioma (WHO III) with the tumor borders delineated by activity >1.6 times the background in the healthy brain. The PET reconstruction is performed applying four different attenuation correction strategies using either CT (a low-dose CT performed on a separate PET/CT scanner), Dixon water–fat separation (DWFS), ultrashort echo time (UTE) or RESOLUTE that identifies bone signal in the MRI. RESOLUTE (white) most accurately resembles CT attenuation correction (black) regarding both tumor volume and maximal tumor uptake relative to a background region (T _max/B). DWFS and UTE significantly overestimate volume and signal intensity and warp the configuration of the tumor due to radial error. The images were kindly provided by Claes Nøhr Ladefoged

Fig. 7

Motion correction of prolonged FET PET/MRI acquisitions. Coronal (top) and transaxial sections (bottom) of FET PET reconstructions from 20 to 40 min post-injection of a 9-year-old boy with giant cell glioblastoma (WHO IV). Markerless motion tracking (Tracoline, version 2) showed periodical head movements of 10–15 mm during the 40 min dynamic FET PET acquisition. Using continuous tracking data, motion correction (MC) at a motion threshold of 5 mm was performed (right side), identifying and aligning a total of four subframes. In motion-corrected images, T _max/B increased from 2.3 to 2.8 (19%) and the biological tumor volume increased from 7 to 11 cm³. Data were kindly provided by Andreas Ellegaard and Jakob Slipsager