Single-photon emission computed tomography (SPECT) imaging has evolved rapidly during the past decades since the introduction of the Anger camera in 1970, the posterior rotating gantry and dual detectors with better reconstruction processes, and quantitative data analysis. In the late 1990s, hybrid SPECT/CT imaging appeared to improve diagnostic accuracy with precise anatomical location and image quality with attenuation correction. In the last 10 years, the improvements in this equipment and the evolution in radiopharmaceuticals have allowed us to improve in the evaluation of physiological processes and in the characterization of pathologies based on morphological patterns [1]. Conventional analog technologies have advanced to multidetector devices with direct conversion digital detectors that improve efficiency, resolution and image quality, resulting in faster studies with lower doses and even the ability to image multiple radionuclides simultaneously. This includes the last generation cadmium-zinc-telluride (CZT) scanners, which bring more possibilities in research and clinical practice, especially in nuclear cardiology [2–4]. There is no denying that SPECT is still the go-to choice for most cardiologists.

There are multiple SPECT/CT applications, and in this chapter, we introduce most of them with demonstrative examples. In tumor pathology, its best-known applications are the evaluation of bone tumors, especially osteoblastic metastases, neuroendocrine tumors, and parathyroid adenomas [5, 6]. However, there are other multiple uses such as the evaluation of hepatocellular carcinoma, liver metastasis, neuroblastoma, paraganglioma, and thyroid cancer. In non-tumor bone pathology, it is indicated in trauma, degenerative disease, and infection, for example – also in the evaluation of benign thyroid pathology, gastrointestinal bleeding, lymphatic system pathology, and pulmonary physiology, among others [5, 7–9]. SPECT systems as well as radiopharmaceuticals are more available and probably cost-effective than PET, so they remain and will remain at the forefront.

1 Tumors

1.1 Hepatocellular Carcinoma

1.1.1 Case 1

A 51-year-old man with a diagnosis of hepatocellular carcinoma. Selected SPECT (top) and SPECT/CT (bottom) of the liver with ^99mTc-MAA particles injected into a hepatic arterial catheter showed several focal areas of slightly to moderately increased activity in the right and left hepatic lobes corresponding to multicentric hepatoma. Only 50% of hepatomas can be imaged with FDG-PET, mainly because of the high levels of phosphatase that dephosphorylate FDG and allow it to diffuse out of cells (Fig. 1) [10].

1.2 Liver Metastases

1.2.1 Case 1

A 68-year-old female patient with liver metastasis from breast cancer. Selected SPECT (top) and SPECT/CT (bottom) of the liver with ^99mTc-MAA into the hepatic arterial catheter showed markedly heterogeneous activity in the liver caused by known metastases. There was no extra hepatic activity (Fig. 2) [11].

1.2.2 Case 2

Selected SPECT (top) and SPECT/CT (bottom) of the upper abdomen with ^99mTc-MAA particles into a hepatic arterial catheter showed curvilinear activity along the gastric wall, indicating the suboptimal position of the hepatic arterial catheter (Fig. 3) [12].

1.2.3 Case 3

A 57-year-old female patient with hepatic metastasis of breast cancer. Selected SPECT (top) and SPECT/CT (bottom) images of the liver with ⁹⁰Y microspheres injected into a hepatic arterial catheter showed increased activity in the right and left hepatic lobes, corresponding to metastatic lesions (Fig. 4) [13].

1.3 Neuroendocrine Tumors

1.3.1 Case 1

A 51-year-old male patient with chest tightness and dyspnea. He had prior history of a pancreatic neuroendocrine tumor, so ¹¹¹In-octreotide SPECT/CT was done. Images showed focal increased activity in a soft tissue mass at the pericardium, which was posteriorly confirmed to be a metastatic lesion (Fig. 5) [14].

1.3.2 Case 2

A 72-year-old male patient with a history of midgut carcinoid. He attended with right shoulder and abdominal pain. ¹¹¹In-octreotide SPECT/CT was performed, finding focal increased activity in the right glenoid at a slerotic lesion and the right hepatic lobe at a large necrotic mass. Posterior biopsy confirmed the diagnosis of metastatic neuroendocrine tumor (Fig. 6) [15].

1.3.3 Case 3

A 71-year-old male patient with abdominal pain, diarrhea, and elevated chromogranin A. ¹¹¹In-octreotide SPECT/CT was performed, finding marked increased activity in a large pancreatic tail mass, as well as diffuse, increased activity in the portal vein. Surgical resection confirmed the diagnosis of a pancreatic neuroendocrine tumor with portal vein invasion (Fig. 7) [16].

1.3.4 Case 4

A 62-year-old female patient with a history of midgut carcinoid. She presented with cough, dyspnea, and abdominal pain, so ¹¹¹In-octreotide SPECT/CT was done. Images showed a large mass in the right adrenal gland without abnormal increased activity. Also, diffuse, increased activity was noted in a consolidation at the right upper lung. Posterior biopsy of both lesions confirmed a right adrenal carcinoma and a metastatic neuroendocrine tumor in the right upper lung (Fig. 8) [17].

1.3.5 Case 5

A 54-year-old female patient with a history of rectal carcinoid. She developed abdominal pain and elevated serum levels of chromogranin A were found. ¹¹¹In-octreotide SPECT/CT was performed, finding multifocal increased uptake in the right hepatic lobe at several biopsy confirmed metastasis (Fig. 9) [18].

1.3.6 Case 6

A 74-year-old female patient with abdominal pain and diarrhea. ¹¹¹In-octreotide SPECT/CT was done, finding focal increased activity in the pancreatic head. The surgical diagnosis was a pancreatic neuroendocrine tumor (Fig. 10) [21].

1.3.7 Case 7

A 67-year-old male patient with hypertension, abdominal pain, and palpitations. Elevated urinary catecholamines were found, so ¹²³I-MIBG SPECT/CT was performed. Images showed focal increased uptake in a left adrenal mass which was confirmed as a pheochromocytoma (Fig. 11) [22].

1.3.8 Case 8

A 68-year-old female patient with a history of midgut carcinoid developed chest pain and dyspnea. Chest X-ray showed a newly developed lung nodulex nodule and she had elevated serum levels of chromogranin A, so ¹¹¹In-octreotide SPECT/CT was done. Images showed focal increased uptake in the right upper lung nodule, which was confirmed to be a metastatic neuroendocrine tumor (Fig. 12) [25].

1.3.9 Case 9

A 64-year-old female patient with a neuroendocrine tumor in the pancreatic tail. Selected SPECT (top) and SPECT/CT (bottom) images of the upper abdomen with ¹¹¹In-octreotide showed a focal area of slightly increased activity in the pancreatic tail. No other lesions were observed (Fig. 13) [27].

1.3.10 Case 10

A 41-year-old male patient with a history of carcinoid tumor, who attended for a regular check-up. ¹¹¹In-octreotide SPECT/CT was done, finding focal increased activity in the middle to lower abdomen corresponding to mesenteric lymph node metastases, as well as in two metastatic lesions in the right hepatic lobe (Fig. 14) [30].

1.3.11 Case 11

A 39-year-old male patient with biopsy-proven lung carcinoid, who underwent ¹¹¹In-octreotide SPECT/CT for staging. Images showed focal increased activity in the right hilum at the primary tumor, without definite uptake in post-obstructive atelectasis (Fig. 15) [32].

1.3.12 Case 12

A 51-year-old female patient with a biopsy confirmed diagnosis of transverse colon neuroendocrine tumor. ¹¹¹In-octreotide SPECT/CT was performed for staging, finding only focal increased uptake in the primary lesion at the proximal transverse colon (Fig. 16) [33].

1.4 Neuroblastoma

1.4.1 Case 1

A 3-year-old girl with confirmed diagnosis of retroperitoneal neuroblastoma. ¹²³I-MIBG SPECT/CT was performed for further evaluation. Images showed focal increased uptake in a retroperitoneal mass adjacent to the left psoas muscle, corresponding to the primary tumor. Neuroblastoma is a neural crest cell tumor arising from the sympathetic chain, commonly in the adrenal gland, and the mean age at the diagnosis was 2 years. Metastases may be found in 75% of these patients. Meta-iodobenzylguanidine (MIBG) is similar to norepinephrine and is taken up by chromaffin granules that are in neuroblastoma and pheochromocytoma (Fig. 17) [35].

1.5 Paraganglioma

1.5.1 Case 1

A 59-year-old male patient, who attended with hypertension and perspiration. Elevated levels of urinary catecholamines were found, so ¹²³I-MIBG SPECT/CT was done for further evaluation. Images showed focal increased activity in a retroperitoneal mass at the aortocaval space, as well as in the left kidney superior pole. The surgical diagnosis confirmed a primary renal paraganglioma with retroperitoneal metastasis (Fig. 18).

1.5.2 Case 2

A 57-year-old female patient with a history of left adrenal paraganglioma, who attended for routine check-up. ¹²³I-MIBG SPECT/CT was performed, showing heterogeneous activity in the liver, with a focal nodular increased uptake in segment 5 (V). Heterogeneous activity in the liver is physiologic and related to timing of the imaging and radiotracer metabolism and excretion through the biliary system. However, focal increased uptake is an abnormal finding, and in this case, it corresponded to a metastatic lesion. Also, an active metastasis was found in the T8 vertebral body (Fig. 19) [36].

1.6 Thyroid Cancer

1.6.1 Case 1

A 59-year-old male patient with a history of thyroid cancer, who underwent coronary CT, finding incidentally multiple lung nodules. ¹³¹I SPECT/CT showed moderately to intense increased iodine uptake in the nodules, confirming metastatic disease. Iodine therapy with 200 mCi of ¹³¹I was administered (Figs. 20, 21, 22 and 23) [37].

1.6.2 Case 2

A 34-year-old female patient with thyroid cancer, who underwent total thyroidectomy with central neck dissection. On ¹³¹I ablation scan, bone metastases were found, which were treated with 250 mCi of ¹³¹I. Post-treatment iodine scan and SPECT/CT were taken, showing intense focal iodine uptakes at T4 and T6, confirming iodine-avid bone metastases (Figs. 24, 25, 26, 27, 28, and 29) [38].

1.6.3 Case 3

A 62-year-old female patient with thyroid cancer history, who was treated with thyroidectomy 6 months earlier. She attended a routine follow-up without symptoms and normal serum levels of thyroglobulin. Selected SPECT (top) and SPECT/CT (bottom) with ¹³¹I demonstrated a focal area of moderately increased activity in the left thyroid bed, which was confirmed to be residual functioning thyroid tissue (Fig. 30).

1.7 Parathyroid Adenoma

1.7.1 Case 1

A 63-year-old male patient with hypercalcemia and weight loss. Laboratory tests showed abnormal serum calcium, phosphorus, and parathyroid hormone levels, so primary hyperparathyroidism was suspected. ^99mTc-MIBI SPECT/CT was performed finding focal delayed uptake in the lower aspect of the right thyroid lobe, corresponding to a parathyroid adenoma, type E (Figs. 31, 32, 33, 34, and 35) [40, 41].

1.7.2 Case 2

A 63-year-old female patient with suspicion of parathyroid adenoma, who underwent ^99mTc-MIBI SPECT/CT. Images showed a focal area of moderately increased activity in the right lower anterior mediastinum, which was confirmed as a parathyroid adenoma, type F (Fig. 36) [42].

1.7.3 Case 3

A 71-year-old female patient with primary hyperparathyroidism, who underwent ^99mTc-MIBI SPECT/CT. Images showed a focal moderately increased activity in the right paraesophageal area at the level of the thoracic inlet, which corresponded to a parathyroid adenoma, type F (Fig. 37) [42].

1.7.4 Case 4

A 56-year-old male patient with confirmed diagnosis of a parathyroid adenoma (type E). Selected SPECT (top) and SPECT/CT (bottom) of the neck and chest with ^99mTc-MIBI were performed. Images showed a focal moderately increased activity in the right paratracheal area at the level of the right inferior thyroid bed (Fig. 38) [42].

1.7.5 Case 5

A 63-year-old female patient with suspicion of a parathyroid adenoma (type C). Selected SPECT (top) and SPECT/CT images of the neck and chest with ^99mTc-MIBI showed a focal moderately increased activity in the right paraesophageal area, confirming the diagnosis (Fig. 39) [42].

1.8 Mesothelioma

1.8.1 Case 1

A 69-year-old male patient with chest pain and dyspnea. The diagnosis of a mesothelioma was confirmed and ^99mTc-MAA SPECT/CT was performed during staging. Images showed slightly decreased activity in the right upper and middle lobes as well as moderately decreased activity in the right lower lobe. Also noted were perfusion defects along the posterolateral periphery of the right lower lobe owing to nodular pleural lesions (Fig. 40) [43].

1.9 Bone Tumors

1.9.1 Case 1

A 10-year-old girl with a history of ossifying fibroma, who underwent ^99mTc-methylene diphosphonate (MDP) SPECT/CT during a follow-up. Images showed moderately increased activity in the bilateral maxillary sinuses and right mandible at expansile bone lesions with fibrous matrix and peripheral sclerotic rim. Ossifying fibromas are benign bone tumors and occur often in children under 10 years in the tibia, femur, mandible, maxilla, and nasal areas (Fig. 41) [45].

1.9.2 Case 2

A 76-year-old male patient with lower back pain. ^99mTc-MDP SPECT/CT showed focal increased uptake at bilateral L5-S1 facet joints, with degenerative changes. Additionally, a focal increased uptake was noted at the superior aspect of the left iliac bone, corresponding to a non-aggressive bone lesion with a central hipodense nidus surrounded by sclerotic bone changes, which was confirmed to be an osteoid osteoma (Fig. 42).

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