Hybrid positron emission tomography/magnetic resonance image (PET/MRI) has undergone rapid evolution during the last years, moving from a predominantly research field to clinical practice. With the advances in faster silicon photomultiplier detectors, MRI-based attenuation correction, and image reconstruction, significant improvements in equipment and image quality have been achieved. Currently, there are fully integrated PET/MRI systems that allow simultaneous and more rapid acquisition, improving not only the technical quality but also the experience for patients who need a low radiation dose [1–3]. With this technology comes the possibility of performing multiparametric MRI studies, where detailed anatomical evaluation and functional evaluation are possible, not only considering the qualitative and quantitative data of PET but also integrating multiple parameters such as perfusion (contrast-enhanced sequences), cellularity (diffusion-weighted sequence), metabolites (spectroscopic analysis), and texture analysis. Additionally, recent developments are very promising in giving the possibility of incorporating advanced data and biomarkers to integrate with bioinformatics and allow a better understanding of the disease, as well as an efficient evaluation, prediction of response to treatment, and follow-up [4–7].

With the growing availability of PET/MRI, its main and differential applications have also been clarified. Nonspecific ¹⁸F-fludeoxyglucose (FDG) PET/MRI continues to be the most widely used, and thus new radiotracers are expanding the field to be explored. Among the most frequent applications of ¹⁸F-FDG PET/MRI, where its superiority over PET/CT has been demonstrated, are the evaluation of head and neck, colorectal, gynecological, bone and soft tissue tumors, as well as the evaluation and characterization of primary or secondary liver lesions [8–12]. It has also shown good results in non-tumor pathology such as epilepsy, inflammatory bowel disease, and cardiac sarcoidosis [4, 13].

The creation of new radiotracers that can be imaged both with PET/MRI and PET/CT, depending on the case and availability, has allowed great advances in the evaluation of other oncological and non-oncological pathologies. In the case of neuroendocrine tumors and prostate cancer, targeting somatostatin receptors with ⁶⁸Ga-DOTATOC, targeting PSMA with ⁶⁸Ga-PSMA-11 among others available tracers, and the inclusion of ¹⁷⁷Lu agents have revolutionized the diagnosis and treatment of these pathologies respectively [14, 15]. In the field of neuroimaging, the wide availability of radiotracers has made it possible to improve the evaluation of multiple targets different from glucose metabolism (FDG), such as DNA synthesis (¹⁸F-fluorothymidine), protein synthesis (¹¹C-methionine, ¹⁸F-fluoroethyl-L-tyrosine [FET], ¹⁸F-fluoro-L-3,4-dihydroxyphenylalanine [DOPA]), and hypoxia (¹⁸F-fluoromisonidazole) [16, 17]. In the field of degenerative diseases, where much remains to be explored and research is very promising, examples of emerging invaluable applications are amyloid PET and Tau PET for Alzheimer’s disease, as well as ¹⁸FP-CIT PET for Parkinson’s disease [18, 19].

In this chapter, we present multiple demonstrative examples of the different uses of PET/MR, with the most relevant anatomical references for each case.

1 Head and Neck

1.1 Case 1

A 75-year-old male patient, with worsening dizziness and weakness in both legs. Brain malignancy was suspected on brain CT, so ¹⁸F- FDG PET/MR was performed. Images revealed marked increased activity in a well-defined enhancing mass involving the corpus callosum, crossing the midline and with subependymal extension. Primary central nervous system (CNS) lymphoma was suspected, and stereotaxic biopsy confirmed a diffuse large B-cell lymphoma (Fig. 1) [20].

1.2 Case 2

A 72-year-old man with diagnosis of lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) from marginal zone lymphoma, with central nervous system involvement. After surgery and chemotherapy, complete response was achieved, but the patient attended an early checkup with headache, so ¹⁸F-FDG PET/MR was performed. Images showed focal increased activity in a lobulated mass at the periventricular white matter, adjacent to the posterior horn of the left lateral ventricle with perilesional edema, which showed predominantly low signal on T2WI and heterogeneous contrast enhancement, which are frequent findings of lymphoma involvement. With these findings, a relapse was confirmed, and treatment was initiated again (Fig. 2) [21].

1.3 Case 3

A 5-year-old patient with gradual loss of vision in the right eye. Clinical examination and contrast-enhanced MRI were performed and confirmed the diagnosis of retinoblastoma. ¹⁸F-FDG PET/MR was performed during initial workup and staging. Minimal uptake was found in the primary tumor and the presence of metabolically active metastases was ruled out (Fig. 3) [22].

1.4 Case 4

A 49-year-old woman with a headache and decreased mobility of the right eye. ¹⁸F-FDG PET/MR was performed, and images showed a metabolically active mass with heterogeneous enhancement in the olfactory recess involving the cribriform plate and ethmoid air cells. The lesion produced lateral displacement of the right medial rectus muscle, compression of the optic chiasm, and obstruction of the sphenoid sinuses. Subsequent biopsy confirmed the diagnosis of an olfactory neuroblastoma, also known as esthesioneuroblastoma (Fig. 4) [23].

1.5 Case 5

A 48-year-old male patient with progressive proptosis, impaired visual acuity, and headaches. ¹⁸F-FDG PET/MR was performed, finding diffuse metabolically active infiltration of the soft tissues in both orbits and eyelids, with encasement and displacement of the optic nerves and muscles, without infiltration. Biopsy revealed the diagnosis of an extra nodal marginal zone B-cell lymphoma (EMZBC) (Fig. 5) [22].

1.6 Case 6

A 55-year-old male patient with sore throat and a soft tissue mass in the right nasopharyngeal wall on physical examination. Biopsy revealed nasopharyngeal squamous cell carcinoma, so ¹⁸F-FDG PET/MR was performed for staging. Images showed increased metabolic activity in the right nasopharyngeal area at a soft tissue mass, consistent with the primary tumor. Hypermetabolic, enlarged, metastatic lymph node (LN) was also found in the right neck, level II (Figs. 6 and 7) [24].

1.7 Case 7

A 55-year-old female patient with a growing ulcerated mass in the right sublingual area. Biopsy was performed confirming an adenoid cystic carcinoma with cribriform pattern, so ¹⁸F-FDG PET/MR was performed for staging. Images showed a focal hypermetabolic lesion in the right sublingual space, displacing the tongue’s intrinsic muscles, without infiltrating them. Ipsilateral, level II, hypermetabolic lymph node metastasis was also found (Fig. 8) [10].

1.8 Case 8

A 55-year-old male patient with a history of persistent dysphagia and cough. Direct endoscopic examination was performed finding a laryngeal mass, consistent with an epiglottic squamous cell carcinoma. ¹⁸F-FDG PET/MR was performed for staging, finding a prominent hypermetabolic mass in the superior aspect of the epiglottis, projecting towards the upper airway and decreasing its caliber. No hypermetabolic lymph nodes or distant metastases were observed (Fig. 9) [10].

1.9 Case 9

A 21-year-old man with a non-painful, progressively growing right parotid mass. Ultrasound-guided biopsy revealed a secretory carcinoma, so ¹⁸F-FDG PET/MR was performed for staging. Images showed a hypermetabolic irregular mass involving both the superficial and deep lobes of the right parotid gland, without associated metastatic lymph nodes (Fig. 10) [25].

1.10 Case 10

A 57-year-old man with a painful, rapidly growing left cervical mass. Ultrasound was performed finding an enlarged, necrotic lymph node, which biopsy revealed a metastatic carcinoma. ¹⁸F-FDG PET/MR was performed suspecting primary head and neck malignancy, and images showed a hypermetabolic mass in the hypopharynx, predominantly left side, with multiple metastatic lymph nodes in the left neck. The diagnosis of primary squamous cell carcinoma in this location was confirmed (Fig. 11) [10].

1.11 Case 11

A 22-year-old man with headache, occasional fever, and weakness in both arms. Laboratory tests did not show definite abnormalities, so ¹⁸F-FDG PET/MR and MRI were performed to rule out unknown origin infection vs occult malignancy. Images showed diffusely increased activity along the spinal cord with corresponding ill-defined high signal intensity lesions in T2WI. With these findings and other neurological tests, the diagnosis of acute disseminated encephalomyelitis (ADEM) was confirmed (Fig. 12) [26].

1.12 Case 12

A 67-year-old male patient with a history of left maxillary sinus squamous cell carcinoma, treated 9 years ago with radiotherapy and surgery (resection with flap reconstruction). He attended his annual checkup completely asymptomatic and among other studies ¹⁸F-FDG PET/MR was performed. Images showed focal increased activity in the lateral wall of the left nostril on the medial aspect of the surgical flap, which also presented heterogeneous contrast enhancement, which was not evident in the previous study. This finding was confirmed as a local recurrence (Fig. 13) [10].

2 Chest

2.1 Case 1

A 62-year-old male patient with a solitary pulmonary nodule and history of heavy smoking. ¹⁸F-FDG PET/MR was performed during staging. Images showed moderately increased activity in a small solid nodule at the left lower lobe, which was later resected and confirmed as an adenocarcinoma. No metabolically active metastases were detected (Figs. 14, 15, 16, 17, 18, and 19) [27, 28].

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