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Chapter 17

Pediatric Nuclear Medicine

David Gilday Introduction

Nuclear medicine studies have an important role to play in the diagnosis, treatment and follow-up of several pediatric conditions and the use of radiopharmaceuticals for diagnostic testing in children is increasing. Although general imaging principles are reviewed in the related "adult" chapters, special technical challenges and a very different spectrum of disorders warrant a separate discussion for children. This chapters highlights selected clinical problems in pediatric nuclear medicine.

Technical Considerations

Environment

When examining children, consideration must be given to patient motion, fear, and parental involvement. The study and approach to the exam must be tailored to the child's problem.

Children are much more aware than is generally appreciated—and thus the goal should be to provide a quiet and friendly environment. The staff should behave in a calm, relaxed manner with a kind, confident and sympathetic approach towards the child. Each study done should be designed to minimize the length of time the child must lie still. Therefore, long dynamic studies such as gastric emptying and transit studies are modified to sequential static images allowing the child to move between images.

All children old enough to comprehend (usually about age three) should have their procedure explained to them in simple words appropriate to their level of understanding. It is also important to gain the parent's cooperation as the parent's attitude can positively or negatively influence their child. Positive aspects of the study should be emphasized, negative aspects minimized. However, it is crucial never to mislead the child about what is about to happen. A child's trust in the staff may be difficult to obtain; once gained it is easily jeopardized. The most valuable distracter is a television, a VCR and a good video. Soothers and sticker awards for being injected all help to make it easier to get a first class result.

Parents should be present unless the procedure requires a sterile field. It has been our experience that with well-trained staff and cooperative parental involvement, it is rare that there is a problem with the study. Occasionally, a child may be a disciplinary problem and is more uncooperative when a parent is present. In these circumstances we ask that the parent stay in the waiting room.

Careful restraint is frequently necessary in the younger patient but should be used in moderation. The goal is to prevent motion as well as an accidental fall from

Nuclear Medicine, edited by William D. Leslie and I. David Greenberg. ©2003 Landes Bioscience.

an imaging stretcher or couch. Children are best immobilized with restrainers strapped around the stretcher top using Velcro straps.

Sedation

If moderate restraint is not successful then sedation is required for a technically satisfactory study. This is especially true for lengthy procedures such as SPECT or whole body imaging. Sedation is recommended in overly anxious patients who refuse to cooperate, very young or hyperactive patients who are unable to remain still, and retarded patients who lack the mental capacity to follow simple instructions.

Sedation may take several forms. In the correct setting, sedation with intravenous pentobarbital sodium (Nembutal®) is very effective. Using a dose of 5 mg kg-1 (to a maximum of 100 mg), we administer half the volume rapidly, wait 60 seconds and then administer a quarter of the dose. This usually puts the child to sleep in about two to three minutes. If not, the remaining quarter dose is given. The child remains asleep for about 45-60 minutes. The advantages of this technique are that the child falls asleep very quickly, the effect is more reliable than with intramuscular injection, and the child recovers faster. As with all sedatives, cardiac and respiratory status must be closely monitored by appropriately trained individuals. We currently use an automated pulse oximeter.

Pentobarbital is contraindicated in neonates less than 2 months of age. This group lacks adequate levels of the liver enzymes required to metabolize pentobarbital. In place of pentobarbital we use an elixir of promethazine (Phenergan®) and chloral hydrate administered 30-45 minutes before scanning. While the effect is less pronounced than with pentobarbital, it is usually adequate and the patient arouses readily. Midazolam (Versed®) orally is useful in some cases.

Diazepam (Valium®) and pentobarbital suppositories have all been found to be inadequate. None produces the deep sleep required to perform nuclear medicine procedures on the patient.

Injection Techniques

Radiopharmaceutical injection in small children presents several minor difficulties, all of which are easily overcome by modifying adult techniques. Children may be completely covered by the head of a large field of view camera. This increases the child's anxiety and makes injection difficult. This is resolved by placing the child supine on the gantry or stretcher top and having the camera underneath. In smaller children, for head, feet or hand imaging, holding the child directly on the camera collimator is a very good technique.

Finding a suitable vein for intravenous injections is rarely a problem. Although the antecubital fossa frequently has the largest vein, the elbow is less easily immobilized than the hand or foot which are the preferred injection sites. With procedures requiring repeated blood samplings (e.g., GFR determination), the insertion of an intravenous catheter is the best approach.

Radiopharmaceutical Dosage

The amount of radioactivity administered can be readily calculated by referring to a chart, using body surface area estimated from the patient's weight and height. The percentage of the standard adult dose is then determined according to the patient's body surface area. This dose calculation is preferred to using weight alone since it results in equal tracer concentration per unit area of planar organ imaging.

It is very important to establish a minimum dose for each radiopharmaceutical. To get an adequate study, especially a dynamic one, there have to be enough photons detected to adequately assess the patient's problem. It is better to accept a slightly higher delivered radiation dose than to have an uninterpretable study. This is especially true in children where one wants the imaging time to be as short as possible in order to avoid motion. The risk of the higher radiation dose is negligible, especially if we have contributed to an accurate diagnosis.

Image Evaluation

It is mandatory to view all images on the imaging workstation using its windowing capability. In musculoskeletal imaging, it is very important to see the physes (growth plates) clearly as well as the diaphyseal long bones which can only be properly performed with multiple window level settings. Reviewing a dynamic study on the workstation is valuable. For example, in voiding cystography a "whiff" of reflux not apparent on hard copy is easily appreciated on the monitor display.

Clinical Role in the Assessment of Childhood Musculoskeletal Disorders

In benign bone diseases the two major indications for nuclear imaging are pain and fever/infection. Plain film examination should be carried out first. Frequently, CT is done to detect and characterize a lesion. The usual bone scanning technique is to acquire blood pool images and static or SPECT images of the areas of clinical interest. The highest resolution system available is used to obtain the best quality images in small children and infants. Magnification with converging or pinhole collimation is frequently used.

Osteomyelitis

The child with osteomyelitis may present with joint pain or tenderness, limited range of motion, soft tissue swelling, erythema, fever or bacteremia. Differentiation of osteomyelitis from cellulitis or septic arthritis may be difficult clinically, and unfortunately, the plain film examination is often non-diagnostic. Frank radiographic bone changes of osteomyelitis are rarely seen due to early diagnosis and treatment. The combined use of blood pool and bone scintigraphy makes it possible to differentiate osteomyelitis from cellulitis.

The typical appearance of osteomyelitis is a well-defined focus of increased bone metabolism associated with an identical area of hyperemia in the blood pool images (Fig. 1). This is most often located in the metaphysis of a long bone. Occasionally other bones are involved, especially if a puncture wound has occurred. This appearance is specific for osteomyelitis and is readily differentiated from the patterns of cellulitis and septic arthritis. However there is some evidence that the technique has less sensitivity in infants of less than 44 weeks gestational age.

The hyperemia involving the metaphysis of the long bone is usually seen between 24 and 36 hours after the onset of symptoms, whereas bone scintigraphy usually becomes positive between 36 and 72 hours. If the findings are not typical of osteomyelitis then gallium imaging is used to determine whether or not infection is present (Fig. 2).

Figure 1. Acute osteomyelitis. (A) Anterior blood pool of the knees, (B) delayed anterior bone scan of the knees and (C) delayed medial bone scan of the right knee following injection with 99mTc-MDP. There is increased blood pool activity and delayed uptake in the metaphysis of the right femur (arrows). Note the loss of demarcation of the physis and the metaphysis. The location and appearance of the abnormality are typical of acute osteomyelitis.

Figure 1. Acute osteomyelitis. (A) Anterior blood pool of the knees, (B) delayed anterior bone scan of the knees and (C) delayed medial bone scan of the right knee following injection with 99mTc-MDP. There is increased blood pool activity and delayed uptake in the metaphysis of the right femur (arrows). Note the loss of demarcation of the physis and the metaphysis. The location and appearance of the abnormality are typical of acute osteomyelitis.

Cellulitis

Cellulitis has a distinctive appearance, which is a diffuse increase in radioactivity involving both the soft tissues and the bone. This is more readily apparent in the blood pool images than in the bone images. The appearance is due to a diffuse soft tissue hyperemia and is readily distinguished from the appearance described above for osteomyelitis (Fig. 3).

Septic Arthritis

Septic arthritis has a similar appearance to that described for cellulitis but the hyperemia involves both sides of the joint. Subchondral bone on either side of the affected joint has marked increased metabolism. These investigations are usually carried out in conjunction with ultrasound which is very sensitive for detecting the effusions associated with septic arthritis. The two studies should be interpreted together.

Legg-Perthes' Disease

Avascular necrosis of the femoral head (i.e.., Legg-Perthes' disease) is usually detected radiologically. In those patients where the radiographs are normal or show mild capsular distention, the use of MRI has become the main means of evaluating the hip. Bone scintigraphy can be used either as an adjunct to determine degree of viability or to detect avascular necrosis in the presence of an inconclusive MRI study. Bone scintigraphy, especially when using pinhole magnification, remains an excellent technique for detecting avascularity of the femoral capital epiphysis (Fig. 4).

Non-Accidental Trauma

Our socio-medico-legal system has developed an enlightened sensitivity to child abuse. The estimated incidence of reported child abuse has increased from 30/1000 in 1985 to 45/1000 in 1992. The incidence of skeletal injury in these children is approximately 20% and is more common among those under 1 year of age. Fractures

Figure 2. Cellulitis and early osteomyelitis. (A) Blood pool image, (B) delayed bone scan image and (C) gallium image. There is increased blood pool activity and increased gallium uptake (arrows) in the right mid-leg. While on the delayed bone scan image, mild diffusely increased activity is present in the right mid-tibia related to the adjacent soft tissue inflammation, there is a focal abnormality suggestive of osteomyelitis in the right proximal tibial metaphysis that also has increased gallium accumulation (arrowheads). Osteomyelitis was confirmed by aspiration.

Figure 2. Cellulitis and early osteomyelitis. (A) Blood pool image, (B) delayed bone scan image and (C) gallium image. There is increased blood pool activity and increased gallium uptake (arrows) in the right mid-leg. While on the delayed bone scan image, mild diffusely increased activity is present in the right mid-tibia related to the adjacent soft tissue inflammation, there is a focal abnormality suggestive of osteomyelitis in the right proximal tibial metaphysis that also has increased gallium accumulation (arrowheads). Osteomyelitis was confirmed by aspiration.

are usually multiple, involving the long bones, skull, vertebrae, ribs, and facial bones, and usually show different stages of healing. In most pediatric hospitals, the approach is to radiograph the clinically affected body parts. If the suspicion of child abuse arises then a total body radiographic examination is done. After this a total body bone scan is performed to locate any unsuspected bony injuries. Metaphyseal-epiphyseal injury is common. Careful positioning and correct window -level settings are important to avoid the pitfall of "blooming" in the image, which may obscure a mild abnormality. Accurate interpretation will depend on assessment of the intensity and shape of the abnormality. Prime sites of investigation are the ribs, costovertebral junctions, spine, and diaphyses of long bones (Fig. 5). If the bone scan is normal 3 days or more after injury, then the probability of bony injury is very low. Disadvantages

Figure 3. Pneumococcal cellulitis after trauma from a hockey puck. (A) Blood pool image and (B) delayed bone scan of the lower legs. Increased blood pool activity is seen (arrow). While there is mild diffusely increased uptake in the left tibia, no focal area of increased uptake is seen.

of the bone scan include: inability to determine the type, extent, and age of each injury; poor bone accumulation of the 99mTc-MDP in cases of severe malnutrition; and inability to differentiate systemic and metabolic disorders associated with trauma from trauma alone.

If one or more areas are found to be abnormal then high detail, multiple view radiography is performed to confirm the abnormality and to help date it. With greater recognition of this problem, more studies are being performed. Skull radiography is best performed to detect trauma to the calvarium, as the detection of fractures of the flat bones of the skull by bone scan is very poor.

Clinical Role in Childhood Malignancies

Osteogenic Sarcoma

Osteogenic sarcomas usually occur in the metaphyses of long bones, a common site being the distal femur or proximal tibia. The common age range is from 10 to 17 years. Occasionally, several sites may be involved at the time of presentation. The plain film always is abnormal but the appearance can mimic other diseases such as chronic osteomyelitis.

Untreated osteogenic sarcoma has a typical bone scan appearance. It demonstrates an uneven intensely increased distribution of tracer in the metaphysis. The blood pool image shows increased blood volume within the tumor. The flow study however has a markedly increased blood flow when compared to what would be expected from the blood pool image. This is due to the presence of arteriovenous connections with direct arteriovenous shunting (Fig. 6).

Figure 4. Legg-Perthes' disease. The left femoral capital epiphysis is photopenic centrally with revitalizing evidence laterally (arrows). This is the classical appearance of recovering Legg-Perthes' disease. Note the dramatic decrease in activity of the rest of the left leg due to disuse atrophy. X-rays done two months later showed a small dense femoral capital epiphysis typical of Legg-Perthes' disease.

Figure 4. Legg-Perthes' disease. The left femoral capital epiphysis is photopenic centrally with revitalizing evidence laterally (arrows). This is the classical appearance of recovering Legg-Perthes' disease. Note the dramatic decrease in activity of the rest of the left leg due to disuse atrophy. X-rays done two months later showed a small dense femoral capital epiphysis typical of Legg-Perthes' disease.

The use of bone scanning in the follow-up of the primary tumor is limited since the scan remains positive because of ongoing bone remodeling. There is a good correlation however between the initial uptake of thallium-201 or 99mTc-sestamibi and the histological response to treatment. A reduction in thallium or sestamibi uptake after treatment indicates a response to chemotherapy.

Recently, there have been attempts to predict the response to chemotherapy by measuring the washout of 99mTc-sestamibi from the tumour. P-glycoprotein is present in cell membranes and protects cells from a variety of chemotherapeutic drugs by facilitating their washout from the cell. Those tumor cells with a high level of P-glycoprotein will be protected from the accumulation of chemotherapeutic agents.

Figure 5. Non-accidental trauma. (A) Anterior bone scan of the legs with (B) posterior view of the upper body. The child refused to move the left leg. Intense uptake related to a fracture of the distal left tibia is readily seen (A, arrow). An unexpected fractue of the distal left humerus was also detected (B, arrow).

Figure 5. Non-accidental trauma. (A) Anterior bone scan of the legs with (B) posterior view of the upper body. The child refused to move the left leg. Intense uptake related to a fracture of the distal left tibia is readily seen (A, arrow). An unexpected fractue of the distal left humerus was also detected (B, arrow).

99mTc-sestamibi washout is also facilitated by P-glycoprotein and hence the measurement of 99mTc-sestamibi washout during the three hours after injection can provide an index of P-glycoprotein levels and the likelihood of multiple drug resistance.

Lymphoma

Gallium scanning has replaced bone scanning in the evaluation of children with lymphomas (Fig. 7). Bone scanning has no place in the evaluation of childhood lymphoma unless it is being used to evaluate an orthopedic problem. Hodgkin's lymphoma, non-Hodgkin's lymphoma and Burkitt's lymphoma are all quite gallium-avid in children. Both the presenting sites, as well as metastases, are readily identified. A 72 hour scan, performed after laxatives to clear normally excreted bowel activity, usually shows any involvement of abdominal nodes. SPECT can be added to better depict lesions in the abdomen when colonic activity is present.

Neuroblastoma

Neuroblastoma is the commonest non-CNS tumor in childhood and frequently metastasizes to bone. Bone scans are more sensitive than radiographic skeletal surveys and, therefore, should be the primary investigation. Multiple foci of increased activity in the metaphyses of long bones are commonly seen, and involvement of the skull, vertebrae, ribs, pelvis, and long bones may also occur. Symmetric metaphyseal involvement is a frequent but subtle abnormality, especially around the knees and involving both femora and tibiae (Fig. 8). The physis is normally slightly elliptical in infants under 18 months of age and is plate-like in older children. The metaphyseal border is always well demarcated. When the physeal activity is wedge-shaped or

Figure 6. Osteogenic sarcoma. (A) Anterior flow image, (B) anterior blood pool image and (C) anterior delayed bone scan of the knees. Arrows show site of involvement in left distal femur. The blood pool and bone scan images both have decreased activity centrally at the site of the increased flow on the frame from the radionuclide angiogram. This indicates arteriovenous shunting in the core of the rapidly growing sarcoma which is typical of osteogenic sarcoma. The blood pool image does not capture the shunting but does reflect the bone repair in response to the tumor.

Figure 6. Osteogenic sarcoma. (A) Anterior flow image, (B) anterior blood pool image and (C) anterior delayed bone scan of the knees. Arrows show site of involvement in left distal femur. The blood pool and bone scan images both have decreased activity centrally at the site of the increased flow on the frame from the radionuclide angiogram. This indicates arteriovenous shunting in the core of the rapidly growing sarcoma which is typical of osteogenic sarcoma. The blood pool image does not capture the shunting but does reflect the bone repair in response to the tumor.

globular, or if there is blurring of the metaphyseal border, metastasis should be suspected even if the involvement is symmetric.

The primary tumor accumulates bone scanning materials such as 99mTc-MDP in 50%-70% of cases (Fig. 9). When the primary tumor is intra-abdominal, renal abnormalities such as nonfunction, obstruction, or inferior and/or lateral displacement are commonly seen. Blood pool and sequential renal scans should be performed during the first 15 minutes after 99mTc-MDP injection in any child suspected of having neuroblastoma or abdominal tumor.

Metaiodobenzylguanidine (MIBG) is an analog of guanethidine and is taken up by a variety of tumors of neural crest origin including neuroblastoma. 131I-MIBG was first introduced in 1983, but has subsequently been replaced by 123I-MIBG because of the better imaging characteristics of iodine-123. 123I-MIBG is effective in detecting soft tissue or marrow neuroblastoma lesions (Fig. 8). MIBG will also detect most but not all bony lesions. In view of the inability of 123I-MIBG scanning to detect all bony metastases, children with a diagnosis of neuroblastoma must have both 123I-MIBG and bone scanning to stage and monitor their disease.

Clinical Role in Neonatal jaundice

One of the more difficult but rewarding investigations in pediatrics is the evaluation of neonatal jaundice. The problem of differentiating neonatal hepatitis from biliary atresia is extremely difficult to achieve with complete reliability. In neonates with biliary atresia, there is good tracer extraction in the first 60 minutes (extraction fraction usually in excess of 85%) but none is excreted into the duodenum. At twenty-four hours no radiotracer is seen in the bowel (Fig. 10). However, with

Figure 7. Lymphoma. Anterior (left) and posterior (right) whole body gallium scans showing abnormal uptake in both hila (arrowheads). There is normal accumulation in the skeleton, liver and lacrimal glands.

neonatal hepatitis there is typically reduced hepatic extraction and delayed clearance with radiotracer appearing in the bowel within 24 hours. We have found that although no neonate with biliary atresia will excrete the radiotracer, a significant number of babies with neonatal hepatitis will also show no excretion. Therefore, while the

Figure 8. Neuroblastoma. (A) 99mTc-MDP whole body bone scan and (B) 123I-MIBG images of the knees. On the bone scan, abnormal uptake is particularly evident in the long bones where increased metaphyeal uptake (arrow) causes loss of definition of the physis. While the bone scan reflects the response of normal bone to tumor infiltration, the 123I-MIBG scan shows tumor uptake in the left distal femur, left tibia and right femur (arrowheads).

Figure 8. Neuroblastoma. (A) 99mTc-MDP whole body bone scan and (B) 123I-MIBG images of the knees. On the bone scan, abnormal uptake is particularly evident in the long bones where increased metaphyeal uptake (arrow) causes loss of definition of the physis. While the bone scan reflects the response of normal bone to tumor infiltration, the 123I-MIBG scan shows tumor uptake in the left distal femur, left tibia and right femur (arrowheads).

presence of tracer in the bowel eliminates the possibility of biliary atresia, the converse is not true as neonatal hepatitis, bile duct paucity syndrome and total parenteral nutrition (TPN) can cause absent excretion of the radiotracer into the bowel. It is important to premedicate the patient for five days with phenobarbital (2.5 mg kg1

Figure 9. Neuroblastoma. Bone scan showing 99mTc-MDP uptake by the intraabdominal primary (arrow).

twice daily for five days) before injecting the biliary radiopharmaceutical. This approach enhances the likelihood of biliary excretion in cases of neonatal hepatitis.

Clinical Role in Rectal Bleeding

The etiology of rectal bleeding in infants and children is often obscure. In a 10 year period from 1952 to 1962, 801 patients were admitted to our institution with a history of rectal bleeding. Sixty-one patients, in whom all examinations were negative, underwent a laparotomy. A Meckel's diverticulum was present in 24, of which 20 contained ectopic gastric mucosa. Meckel's diverticulum is a common congenital anomaly (0.3-3% in mature individuals); however, a relatively small number of these patients (approximately 20%) have ectopic gastric mucosa within their Meckel's diverticulum.

Figure 10. Biliary atresia. Anterior images following the injection of 99mTc-mebrofenin. While activity accumulates in the liver, the biliary tree is not visualized nor is there excretion into the gastrointestinal tract up to 24 hours. Faint activity in the left abdomen at 4 and 24 hours represents renal accumulation.

Figure 10. Biliary atresia. Anterior images following the injection of 99mTc-mebrofenin. While activity accumulates in the liver, the biliary tree is not visualized nor is there excretion into the gastrointestinal tract up to 24 hours. Faint activity in the left abdomen at 4 and 24 hours represents renal accumulation.

99mTc-pertechnetate accumulates in the mucus producing cells of the stomach. Following injection, there is a rapid increase in radioactivity in the stomach as the pertechnetate is extracted by the gastric mucosa. Renal and bladder activity is present as the kidneys excrete 20 percent of the injected pertechnetate. Early sequential views permit monitoring of the rate of accumulation of pertechnetate in the stomach during the first 15 min. The posterior views at 15 and 30 min demonstrate the location of the renal pelves. Other than these normal structures there should not be any focus of activity throughout the abdomen in the area of the small bowel, although ureters and the iliac vessels are sometimes seen.

In the child with a Meckel's diverticulum, the time sequence of radioactive concentration within the ectopic gastric mucosa parallels that in the normal gastric mucosa of the stomach (Fig. 11). This important feature helps differentiate ectopic gastric mucosa from inflammatory causes, which tend to accumulate the radioactivity at a slower rate, and can help to differentiate an extrarenal pelvis from a Meckel's diverticulum.

Problems can occur in interpreting this study. The early appearance of the radiopharmaceutical in the ureters may simulate a focal lesion posteriorly at the pelvic brim due to a slight holdup at this location while the child is supine. This fades with time and usually disappears during the prone and lateral imaging while on the subsequent anterior views there should not be much activity within the ureter. Occasionally a Meckel's diverticulum may overlie a normal structure containing radioactivity, such as the ureter. In this scenario, the diagnosis of Meckel's diverticulum is difficult unless the bowel moves during the study. If not, a repeat study may show the focal accumulation to have moved. In some patients there is rapid movement of the tracer into the duodenum, which causes confusion; however, the lateral and posterior views help to demonstrate the location of such increased activity. To minimize the excretion of pertechnetate into the lumen of the stomach and to promote retention of tracer by ectopic gastric mucosa, we suggest premedication one hour before the study with ranitidine 5 mg kg-1 to a maximum of 50 mg infused in 20 ml of saline over 20 minutes. Any other lesion which contains ectopic gastric mucosa, such as a duplication of the small bowel, can produce the same time sequence but may assume a different shape. Inflammatory bowel disease such as gastroenteritis or

Figure 11. Meckel's diverticulum. Anterior images at (A) 5 minutes and (B) 30 minutes. 99mTc-pertechnetate is seen in the stomach as well as in the Meckel's diverticulum in the right lower quadrant (arrows).

regional enteritis produces abnormal scans but the distribution of activity is diffuse or the time sequence is different from that in the stomach.

Our results suggest that the pertechnetate abdominal scan detects ectopic gastric mucosa with an accuracy of at least 95 percent. This is a significant improvement over previously published reports, which we attribute to the combination of sequential early imaging, multiple views at 15 and 30 min, and the use of ranitidine.

Clinical Role in Genitourinary Disorders

Pelviureteric Obstruction

The child with pelvi-ureteric obstruction is usually evaluated pre- and post-operatively for the degree of relative renal function, absolute renal function and rate of egress of the radioactive urine from the kidneys. Interestingly, many young children with antenatal hydronephrosis have increased renal mass on the side of the hydronephrosis. This has been confirmed in 99mTc-DMSA studies carried out subsequent to the original diuretic washout study. In cases where an obstructive component to urine flow is suspected, a furosemide (Lasix®) stress test is begun between 10 and 30 minutes after the injection of 99mTc-DTPA or 99mTc-MAG3. Intravenous furosemide (1 mg kg-1 to a maximum of 20 mg) is given and images recorded for 20 min into the computer. The clearance rate is calculated using the computer. This provides a quantitative method for determining the effect of surgery and/or post-operative complications on the renal drainage system. Normally the time to empty one-half of the collecting system activity (T 1/2) is less than 8-10 min. This value may be higher (up to 20 minutes) in grossly dilated pelves or after surgery. In cases where the T1/2 is above 10 minutes, retention at 20 minutes is calculated (counts at 20 minutes divided by the counts at time '0') (Fig. 12). If the patient has a T1/2 of 20 minutes then the retention value at 20 minutes is 50%. The furosemide washout study appears to reflect the state of urinary flow better than the Whitaker test in the post-operative period.

In children who have had repair of a pelviureteric junction obstruction or reimplantation of the ureters as an antireflux surgical procedure, there may be a significant delay of about six months before there is a change in relative renal func-

Figure 12. Diuretic renal scan. (A) delayed posterior images, (B) time activity curves of left renal pelvis and right renal pelvis and (C) ROI around left kidney. 99mTc-DTPA was injected and an initial set of images acquired (not shown). After a delay to allow for filling of the left renal pelvis, furosemide was injected. Visually, the right renal pelvis empties completely and the left renal pelvis partially. The left kidney T 1/2 is 32 minutes with 67% retention at 20 minutes—values that are in the obstructed range.

tion. When evaluated after that time, the kidneys usually function and drain normally.

Several important points have to be made regarding the assessment of diuretic washout curves. Firstly, the T1/2 is invalid when performed on normal kidneys that have already emptied their pelves. Secondly, when there is poor renal function, the kidneys cannot be evaluated as there may be little, if any, response to the furosemide stimulation. Lastly, in large hydronephrotic kidneys of greater than 70 ml capacity, there may be a significant delay in emptying even though there is no mechanical obstruction.

Urinary tract infection

Radionuclide techniques are the primary imaging modalities in evaluating children with suspected upper urinary tract infections (UTI). The direct radionuclide cystogram is the most sensitive method for detecting reflux—a condition which is often a prelude to an upper UTI. Direct radionuclide cystography entails bladder catheterization and instillation of saline mixed with a non-absorbable tracer such as 99mTc-MDP. The detection rate of reflux is as good as or better than that of the voiding cystourethrogram (VCUG) while the radiation dose is significantly less than that of the radiological study. In addition, the bladder and ureters are constantly monitored throughout both filling and emptying, something not feasible using fluoroscopy. Recently, computer analyzed antegrade voiding cystograms have been studied and appear to be almost as accurate as the retrograde version. In this indirect technique, a renal scan is performed and once the kidneys have emptied and bladder filled, continuous imaging is carried out during voiding. This may become the preferred procedure as it is more physiological. However, due to possible pelvic

POSTERIOR SITTING, 20 SEC/FR

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Figure 13. Bilateral vesico-ureteric reflux to the level of the renal pelves is clearly demonstrated.

Figure 13. Bilateral vesico-ureteric reflux to the level of the renal pelves is clearly demonstrated.

Figure 14. Pyelonephritis. 99mTc-DMSA study with planar imaging in the (A) posterior and (B) right posterior oblique projections. A defect is seen in the upper pole of the right kidney (arrows).
Figure 15. Renal scar. 99mTc-DMSA scan with (A) planar quantitation, (B) coronal SPECT and (C) sagittal SPECT images. Scarring is seen in the lower half of the kidney (arrows).

dilatation and thus retention of radioactive urine (which could mask reflux), the most widely accepted method is still direct radionuclide cystography (Fig. 13).

If an upper UTI is suspected, the child must be evaluated to determine whether or not acute pyelonephritis is present. If the child is sick enough to be admitted to hospital, then a 99mTc-DMSA SPECT study should be performed to determine whether or not pyelonephritis is present. Ultrasound should also be performed to see if there is dilatation of the renal pelvis. Finally, a cystogram should be performed to determine if reflux is present. If the child is suspected of having an upper UTI, but is not sufficiently ill to be admitted to hospital, the first study should be a cystogram and if reflux is demonstrated, this should be -followed by ultrasound and DMSA studies. Similarly, if there are repeated UTIs at the time of presentation, this patient should be investigated in the same manner.

Acute pyelonephritis appears as a non-segmental single or multifocal reduction in cortical accumulation of the 99mTc-DMSA (Fig. 14). In the acute phase, it is sometimes difficult to do SPECT imaging and in these cases planar imaging with oblique views is a satisfactory substitute. Subsequent 99mTc-DMSA scans to monitor the progress of acute pyelonephritis should probably be done using SPECT imaging. Our experience is that while SPECT imaging does not increase the sensitivity of diagnosis in acute pyelonephritis, it is useful in defining the location, size and multiplicity of lesions. A major concern after an episode of acute pyelonephritis is the development of scars. In this case, SPECT imaging appears to be the method of choice. Not only is it easier to define whether scars are present or not, but location and definition are also enhanced (Fig. 15). In addition, it is much easier to determine whether an apparent defect toward the upper pole of the left kidney is a true scar or secondary to splenic impression. Cortical mantle thickness is also much more readily defined with SPECT.

Figure 16. Aspiration demonstrated on a radionuclide salivagram with posterior imaging of the chest. For orientation purposes, markers are placed over the shoulders ('M'). A drop of 99mTc-MDP is administered orally with subsequent imaging. The "wishbone" shaped uptake in the chest represents aspiration into the trachea and both mainstem bronchi (arrowheads). Normal swallowed activity is seen in the stomach (arrow).

Figure 16. Aspiration demonstrated on a radionuclide salivagram with posterior imaging of the chest. For orientation purposes, markers are placed over the shoulders ('M'). A drop of 99mTc-MDP is administered orally with subsequent imaging. The "wishbone" shaped uptake in the chest represents aspiration into the trachea and both mainstem bronchi (arrowheads). Normal swallowed activity is seen in the stomach (arrow).

Frequently Asked Questions (FAQ's)

What technique is recommended to detect pulmonary aspiration?

The role of gastroesophageal reflux as the cause of symptoms and more specifically lung disease is well defined. However, it is difficult to determine whether or not the reflux is the cause of the repeated pulmonary infections. In the past the use of 99mTc-labeled milk to monitor reflux and aspiration in children has been used to see if refluxed gastric contents are aspirated. We have been much more successful using the salivogram, which is performed by instilling a drop of radiotracer (any 99mTc-radiopharmaceutical will do) in the mouth and letting the child swallow their radioactive saliva. This is carried out three times with dynamic imaging of the thorax and upper abdomen. After the three salivograms, a long exposure (2-3 minutes) image of the thorax is done to detect any aspiration (Fig. 16). This procedure is very physiological as it depends upon the normal pharyngeal motility. In children with cerebral palsy or other neurological disorder that affects pharyngeal mechanics the study can show the presence of aspiration. It is an easy test to do and interpret.

Additional Reading

1. Conway JJ, ed. Pediatric nuclear medicine. Semin Nucl Med 1993; 23:3 and 23:4. These two issues were devoted to pediatric nuclear medicine. Topics of interest include the use of labeled RBCs and WBCs in abdominal disease (Miller JA. 23:219-230), MIBG in children (Gelfand MJ. 23:231-242), scintigraphic classification of Legg-Perthes disease (Conway JJ. 23:274-295), spine pain in children (Sty JR et al. 23:296320) and bone scintigraphy in child abuse (Conway et al. 23:321-333).

2. Cooper JA. Kidney infection in children: Role of nuclear medicine. In: Nuclear Medicine Annual 1998. Philadelphia: Lippincott-Raven Publishers, 1998:225-246. This includes a discussion of radionuclide cystgography as well as renal cortical scintigraphy.

3. Mandell GA. Nuclear medicine in pediatric orthopedics. Semin Nucl Med 1998; 28(1):95-115.

Topics covered include painful hip, the limping preschool child, foot pain in older children, bone infections and back pain in adolescents.

4. Nadel HR. Hepatobiliary scintigraphy in children. Semin Nucl Med 1996; 26(1):25-42.

A thorough discussion of the technical and clinical aspects of hepatobiliary scanning in children.

5. Piepsz A, Blaufox MD, Gordon I, Granerus G, Majd M, O'Reilly P et al. Consensus on renal cortical scintigraphy in children with urinary tract infection. Scientific Committee of Radionuclides in Nephrourology. Semin Nucl Med 1999; 29(2):160-74.

A consensus document on technical and clinical issues related to DMSA imaging for urinary tract imaging in children.

Appendix

Appendix I. Half-lives and principal emissions from common radionuclides

Nuclide Half Life Mode of Energy Abundance

Decay*

133Xe

5.2 days

0 0

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