Gastric Emptying Scintigraphy: SNM Recommendation

Facts: Gastric Emptying Scintigraphy

• Performed to evaluate patients with symptoms suggesting alteration of gastric emptying or motility
• Provide physiologic, noninvasive, quantitative measurement of solid or liquid gastric emptying
• Used to diagnose delayed gastric emptying (ie, gastroparesis) or rapid emptying (dumping syndrome)

Factors affecting gastric emptying (potentially creating false-positive or false-negative tests)

• Medications: prokinetics (shorten gastric emptying), narcotic analgesics (prolong gastric emptying)
• Tobacco smoking (prolong gastric emptying)
• Hyperglycemia (prolong gastric emptying)
• Premenopausal status (prolong gastric emptying)

Standards for performing GES as recommended by Society of Nuclear Medicine (SNM)

• Full recommendation paper (link) provides recommended timing of imaging, composition of meal, glycemic control, monitoring of symptoms and assessment of severity
• Low-fat, egg white meal
• Imaging at a minimum at 0,1,2 and 4 hours after radiolabeled meal ingestion

Spinal Langerhans Cell Histiocytosis (LCH)

Figure 1: Tc-99m MDP bone scan (posterior image) shows a focus of increased activity at L2 vertebral body in a 24-year-old woman presenting with back pain.

Figures 2&3: Axial GRE T2W and sagittal post-contrast T1W MR images show a round focus of bone destruction surrounded by bone marrow edema and enhancement of L2 body, sparing the posterior elements. 

Facts: LCH

• Rare, benign disorder of unknown etiology comprises of eosinophilic granuloma (unifocal), Hand-Schuller-Christian disease (multifocal) and Letterer-Siwe disease (disseminated variant) - these are different manifestations of a same disease
• Clonal proliferation of Langerhans cells
• Peak incidence 5-10 years but there is a shift toward younger children

Spinal LCH

• Vertebral involvement in 8-25% of cases
• Thoracic > cervical, lumbar
• Vertebral body >> posterior elements
• Solitary, well-defined osteolytic lesion with scalloped borders eventually progresses to collapse and a classic "vertebra plana"
• Typically single vertebral body involved. Disc spaces spared
• Soft tissue mass suggests more aggressive course

Main Imaging Differentials of Spinal LCH

• Osteomyelitis
• Ewing sarcoma
• Leukemia, lymphoma, metastatic neuroblastoma

Reference:
Hosalkar HS, Greenberg JS, Wells L, Dormans JP. Isolated Langerhans Cell Histiocytosis of the T12 vertebra in an adolescent. Am J Orthop 2007;36: E21-E24.

Mediastinal Neuroblastoma

Axial CT image at the level of mid thoracic spine of a 5-year-old boy shows a well-circumscribed, enhancing left paraspinal mass located between the medial ends of the ribs. 

An MIBG study (posterior view of the thorax and upper abdomen) shows a focus of moderate uptake in the left side of the lower thorax, corresponding with the site of abnormal mass on CT. Note intense uptake of bilateral adrenal glands. 

Facts: Neuroblastoma

• 8-10% of all childhood malignancies
• Malignant tumor composed of immature ganglion cells. Most (2/3) arise from abdomen or pelvis and the rest is extra abdominal
• Typically seen in children under age of 5 years
• Treatment determined by stage of tumor at presentation. Regionally limited disease is potentially resectable, but locally extensive or disseminated disease is usually not resectable
• Current imaging staging evaluation: 1) CT or MRI of primary tumor, 2) skeletal survey, 3) bone scintigraphy or MIBG for bone metastasis, and 4) bone marrow aspiration and biopsy for marrow disease
• CT alone has low sensitivity (43%) but high specificity (97%) for detection of stage 4 disease. CT accuracy = 81%. MRI is more sensitive (83%) but less specific (88%) and slightly more accurate (85%). 

Imaging Findings: CT/MRI

• Sharply marginated, fusiform paraspinal mass
• Oriented along direction of sympathetic chain
• 40% contain calcifications
• Heterogeneous enhancement
• Differentiation from ganglioneuroblastoma (usually 5-10 years old) and ganglioneuroma (usually > 10 years old) not possible by imaging. Basically, they are tumors of sympathetic ganglia

References
1. Siegel MJ. Pediatric Body CT. 2008
2. Siegel MJ, Ishwaran H, Fletcher BD, et al. Staging of neuroblastoma at imaging: report of the radiology diagnostic oncology group. Radiology 2002;223:168-175. 

Acute Tubular Necrosis

Tc-99m MAG3 renal scan of a renal transplant recipient, day 1 after transplant with oliguria, shows delayed excretion of tracer from the transplant kidney. Images in vascular phase (not shown) are normal (normal perfusion and uptake).

Facts

• May occur immediately or after an initial short period of allograft function
• Related to both donor and recipient factors
• More common in cadaveric kidneys of older donors who sustained warm ischemia time or prolonged hypotensive periods
• Presented with oliguria or anuria early after transplant
• Diagnosis made by exclusion of other factors. Traditional signs (tubular casts, low urine osmolality) not reliable if patients with native partially functioning kidneys
• Treatment: supportive, return to dialysis if anuric (expected recovery of renal function usually within 3 weeks)

Renal Scan

• Normal perfusion, variable uptake but no (or delayed) excretion
• Serial scans helpful in determining viability of oliguric kidneys, predicting recovery or deterioration

Reference:

Resnick MI, Older RA. Diagnosis of Genitourinary Disease, 2nd edition, 1997

Hypertrophic Pulmonary Osteoarthropathy (HPOA)

Bone scan image shows diffuse increased uptake along the periosteum/cortical margins of both tibias (arrows), sparing the epiphysis, in this patient with lung cancer.

Facts: HPOA

• Clinical syndrome that includes clubbing of fingers/toes, periostitis of tubular bones of extremities and arthritis
• Originally described in association with pulmonary lesions
• Most commonly associated with pulmonary tumors (10% of cases)
• Patients can be asymptomatic or present with arthralgia, arthritis or bone pain
• Histopathology shows edema, mononuclear infiltrates and later osteoid formation of the periosteum
• Commonly involves long bones of forearms and legs, spared axial skeleton and skull

Imaging

• Symmetric periostitis along bony shafts, confined to diaphysis; do not involve joint
• Regular and undulating periosteal reaction
• On bone scan, there is diffuse increased uptake along the periosteum or cortical margins of long bones with sparing of epiphysis

Disorders Described with HPOA

• Pulmonary: cancer, metastasis, mesothelioma, infection and bronchiectasis
• Mediastinum: thymic cancer, thyroid cancer, esophageal leiomyoma, Hodgkin's disease
• Heart: cyanotic heart disease, bacterial endocarditis
• Others: liver cirrhosis, inflammatory bowel disease

Reference:

Vigorita VJ, Ghelman B, Mintz D. Orthopaedic Pathology, 2nd edition, 2007.

Chronic Pulmonary Embolism

Fig.1: Perfusion lung scan (posterior view) with Tc-99m MAA shows multiple small peripheral perfusion defects in both lungs. There is a matched defect in the right lung that corresponds to abnormality on chest radiograph (not shown).
Fig. 2: Ventilation scan (posterior view) shows normal ventilation in areas of perfusion defects, except only in the right lung. Combined with perfusion scan findings, there are multiple small mismatches in both lungs and a matched defect in the right lung. This patient was considered having intermediate probability for pulmonary embolism. Subsequent pulmonary CTA did not show an acute PE but evidence of mosaic perfusion, typical of chronic pulmonary embolism.

Facts:

• Natural course of pulmonary emboli includes complete resolution, partial resolution, persistent defects or presence of new abnormalities
• Lung scans may show false positivity in patients with unresolved pulmonary emboli
• Those patients likely to delay clearing of pulmonary emboli: elderly, with underlying chronic lung disease, heart failure or having very extensive pulmonary infarction
• Serial lung scans may be helpful in management of patients with thromboembolic disease(decision whether to continue anticoagulant therapy, new abnormalities may influence more invasive therapy, provision of new baseline)
• If an embolus is going to clear, it will do so by three months. What is left after three months will persist indefinitely

Reference:

Fogelman I, Maisey MN, Clarke SEM. An atlas of clinical nuclear medicine, 1994, 2nd edition.

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Vertebral Burst Fracture

Fig.1: Posterior bone scan image shows a linear increased uptake at T12 (arrow) in an old patient with osteoporosis and low back pain.

Fig.2: Sagittal reformatted CT image reveals a burst fracture involving T12, corresponding with findings on bone scan.

Tc-99m MDP Bone Scan & Osteoporosis

• Bone scan may be helpful in symptomatic osteoporotic patients for identification of cause of back pain
• Negative bone scan rules out a recently occurred osteoporotic fracture
• Positive bone scan (hot spot) mandates further investigation to differentiate between degenerative change, fracture and malignancy
• Linear uptake (like in our case) usually indicates acute/subacute fracture.

Reference:

van Goethem J, van den Hauwe L, Parizel PM. Spinal imaging: diagnostic imaging of the spine and spinal cord, 2007.

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Extraadrenal Pheochromocytoma: I-123 MIBG

Planar image (anterior view) of an I-123 MIBG scan shows intense uptake in the midline of the lower abdomen in a patient with elevated urine metanephrine.

Facts: Pheochromocytoma

• Uncommon tumor arising from pheochromocytes of adrenal medulla, paraganglia near aorta or sympathetic ganglia
• Common in 4th-6th decades of life, men = women
• 10's rule: 10% bilateral, 10% malignant, 10% children, 10% extraadrenal
• Imaging used to localize tumor after laboratory confirmation of elevated urine metanephrine or resting plasma cathecholamine
• I-123 MIBG and/or MRI commonly utilized for localization

I-123 MIBG (meta-iodobenzylguanidine)

• Patient preparation include: suspend all medications that could interfere with MIBG uptake for 5-6 days (i.e., calcium blocker, sympathomimetics, reserpine), use potassium iodine or sodium perchlorate orally 1 day before scanning and continue for 7 days to block thyroid uptake of unbound iodine
• Scan done with planar imaging at 4 and 24 hours after tracer administration (300-370 MBq of I-123 MIBG)
• Diagnosis of pheochromocytoma when 1) adrenal uptake more intense than liver, 2) extra-adrenal focal uptake seen

Imaging Workup Recommendation

Based on a study of 32 patients who underwent CT, MR and MIBG scans (each patient had all three imaging performed for research),

• MRI alone had 93% sensitivity and positive predictive value (PPV)
• MIBG alone had 90% sensitivity and 100% PPV
• MRI + MIBG had 100% sensitivity and PPV

Reference:

Lumachi F, Tregnaghi A, Zucchetta P, et al. Sensitivity and positive predictive value of CT, MRI and I-123 MIBG scintigraphy in localizing pheochromocytomas: a prospective study. Nucl Med Commun 2006;27:583-587.

Nonvisualization of the Gallbladder with HIDA Scan

HIDA (Tc-99m hydroxy iminodiacetic acid) scan shows normal uptake in the liver with excretion into the extrahepatic bile duct (arrow) and in the bowel (arrowheads) at 25-30 minutes after radiotracer injection. Intravenous morphine was administered at 60 minutes. The images obtained up to 2 hours show no activity in the gallbladder.

Facts: HIDA scan

• Also known as hepatobiliary scan
• Liver uptakes HIDA and excretes it into bile that drains into the bowel
• Normal activity should be seen immediately in the liver, at one hour in gallbladder and into the bowel
• The scan can be done to help diagnose acute cholecystitis, postoperative bile leak
• Morphine can be utilized to shorten the examination time for the diagnosis of acute cholecystitis if the gallbladder is not seen at 1 hour but the bile duct and bowel activity is visualized.
• Cholecystokinin or fatty meal can be used to help diagnose chronic cholecystitis.

Findings on HIDA scan

Nonvisualization of gallbladder WITH bowel activity

• Acute cholecystitis
• Previous cholecystectomy
• Non-fasting patient (including IV feeding)
• Severe hepatic disease
• Chronic cholecystitis (usually fills after 1 hour)

Nonvisualization of gallbladder WITHOUT bowel activity

• Biliary obstruction of any cause
• Severe hepatic disease
• Opiates (because of their effect on the sphinctor of Oddi)

Our patient: acute cholecystitis confirmed at surgery

References:

1. Sharp PF, Gemmell HG, Murray AD. Practical nuclear medicine, 3rd edition, 2005.

2. Chapman S, Nakielny R. Aids to radiological differential diagnosis, 4th edition, 2003

Superscan

Figure: Bone scan image shows diffuse increased bone uptake throughout the skeleton with relative absence of kidney uptake (arrows), consistent with "superscan". There are several focal areas of uptake in the ribs, skull (arrowhead), scapulae and extremities indicating metastatic disease in a 73-year-old man with prostate cancer. The patient had a right craniotomy defect seen as a photopenic region on the posterior view.

Superscan "High ratio of bone uptake relative to soft tissue uptake, absent or relatively decreased renal uptake, homogeneous uptake of axial skeleton"

Two Types of Super Scan

1. Metabolic: homogeneous uptake, usually hot at the calvarium, uptake seen at the extremities
2. Metastatic: heterogeneous, usually absent uptake at the calvarium (unless metastatic lesions), uptake at distal extremities usually not seen

Metastatic "Superscan"

• Prostate cancer, breast cancer, lung cancer
• RCC, lymphoma, bladder cancer

Reference:

Morton K, et al. Diagnostic Imaging: Nuclear Medicine. Amirsys, Inc. 2007

Ewing Sarcoma of the Pelvis

Figures 1 & 2: Coronal reformatted CT images of the pelvis of a 16-year-old man show a large heterogeneous soft tissue mass (arrows) involving the right iliac bone. The mass is enhanced and contains ring and arc calcifications. Note lytic lesions in the lumbar vertebral body (arrowhead).
Figure 3: Anterior bone scan image of the pelvis shows focal increased uptake in the right iliac bone and L4 vertebral body, corresponding with findings on the CT scan.

Facts

• First described by Ewing in 1921
• Family of small round cell neoplasms including: 'classic' Ewing sarcoma of bone, extraskeletal Ewing sarcoma, small cell tumor of thoracopulmonary region (Askin tumor), and soft tissue-based primitive neuroectodermal tumors (PNET).
• Currently believed to be due to spontaneous genetic transolocation
• Second most common bone cancer in adolescents and young adults (after osteosarcoma)
• 5-20 years old, male slightly more than female
• Whites much more common than Asians or Africans

Imaging Appearance

• Permeative lytic lesion with soft tissue components
• Ring and arc calcifications (chondroid matrix)
• Codman triangle or onion multi-layered periosteal reaction
• Common locations: pelvic bones (26%), femur (20%), tibia/fibula (18%), chest wall (16%)
• In long bone, diaphysis > metaphysis
• Increased uptake on bone scan

Work-up

• Aim to distinguish localized disease from metastatic disease
• MRI +/- CT of the lesion
• Chest CT to look for pulmonary metastasis
• Whole body bone scan or PET
• Bone marrow biopsy or MRI of the spine
• Tumor at nonaxial skeleton primary site, age <>

Our case: Ewing sarcoma with bone metastases

Reference:

Ludwig JA. Ewing sarcoma: historical perspectives, current state-of-the-art, and opportunities for targeted therapy in the future. Curr Opin Oncol 2008; 20:412-418.

Suspected Pulmonary Embolism in Pregnant Patient (3)

Figure: Axial CT image of the chest (PE protocol) shows filling defects (arrows) in the subsegmental branches of bilateral lower lobe pulmonary arteries in a pregnant woman at her 7-week gestation.

Second-line Imaging Tests

CT Pulmonary Angiography

• Now accepted standard for imaging diagnosis of PE
• In pregnant women, number of nondiagnostic CTPA may be higher than in non-pregnant population given an increased circulatory volume and altered cardiac output
• CT venography portion should be replaced with lower extremity ultrasound to reduce radiation exposure
• Dose reduction methods include (but not limited to): decrease mA, KVP and Z-axis coverage

Lung Scintigraphy

• Consider in patients with normal chest radiograph and no history of asthma or COPD
• Consider in patients with contraindication for iodinated contrast agent ie severe allergic reaction, impaired renal function
• Dose reduction methods include (but not limited to): elimination of ventilation scan if perfusion scan negative, decrease dose of perfusion scan by half

Other Imaging Options

• MRI without gadolinium can be performed by true fast imaging with steady-state precession, but limited evaluation to first-order pulmonary arteries
• Conventional angiography is reserved only for unstable patients needing mechanical clot lysis, or when other tests are nondiagnostic

Reference:

Pahade JK, et al. Imaging pregnant patients with suspected pulmonary embolism: what the radiologist needs to know. Radiographics 2009; 10.1148/rg.293085226 (Published online before print on March 30, 2009)

Suspected Pulmonary Embolism in Pregnant Patient (2)

Potential algorithm for pulmonary embolism diagnosis in pregnant women (adapted from Pahade JK, et al. Radiographics 2009; 10.1148/rg.293085226)

First-Line Imaging Tests

Why Perform Chest Radiography?

• Search for other causes of symptoms
• Use to triage for further test, ie to perform lung scintigraphy or CT pulmonary angiography as the next test
• Normal chest radiograph does not exclude PE

Why Perform Lower Extremity Ultrasound?

• Positive result can be used to justified anticoagulation without further imaging
• Negative result should warrant further imaging in the setting of clinically suspected PE because PE may occur in the absence of DVT, isolated pelvic DVT may occur without DVT in lower extremities
• DVT is more common in the left lower extremity (more than right)

Reference:

Pahade JK, et al. Imaging pregnant patients with suspected pulmonary embolism: what the radiologist needs to know. Radiographics 2009; 10.1148/rg.293085226 (March 30, 2009)

Suspected Pulmonary Embolism in Pregnant Patient (1)

Figure: Transverse ultrasound image of the right femoral vein shows no evidence of deep vein thrombosis in a pregnant patient (7-week gestational age) presenting with acute dyspnea. Her subsequent CT pulmonary angiography shows multiple subsegmental pulmonary emboli.

Pulmonary Embolism in Pregnancy

• One in 1,000 to 10,000 pregnancies in prenatal period
• Risk of PE increases five fold during pregnancy
• Risk of PE increases with successive trimester and puerperal period (some studies demonstrated equal risks among different trimesters)
• Mortality up to 15-30%
• PE is a preventable cause of maternal death

Clinical Problems

• Difficult clinical diagnosis because of several conditions can mimic PE in pregnant patients, including normal physiologic change of pregnancy
• D-dimer assay not helpful if positive

Imaging Diagnosis

• No current standard guideline for imaging of PE in pregnant patients
• Algorithm depends on institutional preference, resource availability and individual radiologist/physician practice pattern
• Usual first-line imaging tests are chest radiography and lower extremity ultrasound

Reference:

Pahade JK, et al. Imaging pregnant patients with suspected pulmonary embolism: what the radiologist needs to know. Radiographics 2009; 10.1148/rg.293085226 (published online ahead of print on March 30, 2009)

Parathyroid adenoma: Sestamibi scan

Tc-99m - sestamibi หรือ ที่เรียกว่า MIBI scan (มิบี่สแกน) อาศัยหลักการที่ว่าสารตัวนี้เมื่อฉีดเข้าเส้นเลือดดำจะผ่านเยื่อหุ้มเซลล์และเยื่อหุ้ม mitochondria ด้วยวิธี passive transport เพราะตัวมันเป็น lipophillic เมื่อเข้าไปอยู่ใน mitochondria จะค้างอยู่ภายในเซลล์ได้เป็นเวลานาน เซลล์ที่มีการผลิตพลังงานมากๆ ซึ่งก็จะมี mitochondria มาก ก็จะจับกับ MIBI ได้ดี เช่น พวกเซลล์มะเร็งส่วนใหญ่ ดังนั้น MIBI จึงถือว่าเป็น non-specific tumor seeking agent ที่ดีตัวหนึ่ง

รูปที่ 1 เป็น MIBI scan ของผู้ป่วย hyperparathyroidism ซึ่ง MIBI จะจับทั้งใน thyroid และ parathyroid จึงอาจมีการทำ thyroid scan ด้วย Tc-99m O4 (pertechnetate) เพื่อเปรียบเทียบ (รูปที่ 2) หรือ นำมาลบ thyroid ออก (subtraction) ไปดังรูปที่ 3

รูปที่ 2 thyroid scan ด้วย Tc-99m O4 (pertechnetate)

รูปที่ 3 เอารูป MIBI ตั้ง ลบด้วย รูป Tc-99m O4 (pertechnetate) จริงๆ แล้วรูป subtraction จะมีประโยชน์มากโดยเฉพาะ เมื่อมี parathyroid adenoma อยู่หลัง thyroid ซึ่งอาจไม่เห็นชัดเท่านี้

อีกตัวช่วยหนึ่งก็คือ dalayed imaging ของ MIBI โดย อาจรอ 2-4 ชั่วโมงหลังจากถ่าย MIBI รูปแรก โดยอาศัยหลักการที่ว่า MIBI จะ wash out ออกจาก thyroid ได้เร็วกว่า parathyroid adenoma (ซึ่งมี mitochondria activity มากกว่า) ก็จะเห็น parathyroid adenoma เด่นชัดขึ้น ดังรูปที่ 4

รูปที่ 4 dalayed MIBI scan

รูปที่ 5 แสดง MIBI scan ในผู้ป่วย parathyroid adenoma อีกราย