TY - JOUR
AU1 - Biassoni,, Lorenzo
AU2 - Easty,, Marina
AB - Abstract Background Nuclear medicine imaging explores tissue viability and function by using radiotracers that are taken up at cellular level with different mechanism. This imaging technique can also be used to assess blood flow and transit through tubular organs. Nuclear medicine imaging has been used in paediatrics for decades and this field is continuously evolving. Sources of data The data presented comes from clinical experience and some milestone papers on the subject. Areas of agreement Nuclear medicine imaging is well-established in paediatric nephro-urology in the context of urinary tract infection, ante-natally diagnosed hydronephrosis and other congenital renal anomalies. Also, in paediatric oncology, I-123-meta-iodobenzyl-guanidine has a key role in the management of children with neuroblastic tumours. Bone scintigraphy is still highly valuable to localize the source of symptoms in children and adolescents with bone pain when other imaging techniques have failed. Thyroid scintigraphy in neonates with congenital hypothyroidism is the most accurate imaging technique to confirm the presence of ectopic functioning thyroid tissue. Areas of controversy Radionuclide transit studies of the gastro-intestinal tract are potentially useful in suspected gastroparesis or small bowel or colonic dysmotility. However, until now a standardized protocol and a validated normal range have not been agreed, and more work is necessary. Research is ongoing on whether magnetic resonance imaging (MRI), with its great advantage of great anatomical detail and no ionizing radiations, can replace nuclear medicine imaging in some clinical context. On the other hand, access to MRI is often difficult in many district general hospitals and general anaesthesia is frequently required, thus adding to the complexity of the examination. Growing points Patients with bone pain and no cause for it demonstrated on MRI can benefit from bone scintigraphy with single photon emission tomography and low-dose computed tomography. This technique can identify areas of mechanical stress at cortical bone level, difficult to demonstrate on MRI, which can act as pain generators. Positron emission tomography (PET) is being tested in the staging, response assessment and at the end of treatment of several paediatric malignancies. PET is becoming more widely utilized in neurology in the pre-surgical assessment of some children with drug resistant epilepsy. Areas timely for developing research The use of PET/MRI scanners is very attractive as it combines benefits of MR imaging with the assessment of cellular viability and metabolism with PET in one examination. This imaging technique will allow important research on tumour in-vivo metabolism (possible applications include lymphomas, neuroblastomas, malignant germ cell tumours andbrain tumours), with the aim of offering a personalized biological profile of the tumour in a particular patient. Ground-breaking research is also envisaged in neurosciences, especially in epilepsy, using PET tracers that would enable a better identification of the epileptogenic focus, and in psychiatry, with the use of radiolabeled neurotransmitters. In paediatric nephro-urology, the identification of the asymptomatic child with ante-natally diagnosed hydronephrosis at risk of losing renal parenchymal function if left untreated is another area of active research involving radionuclide renography. paediatrics, nuclear medicine, radionuclide imaging, paediatric radiology Introduction Nuclear medicine imaging techniques, more recently referred to also as molecular imaging, functional imaging or radioisotope imaging techniques, have been used in children for decades and are well established in paediatric clinical practice. Paediatric nephro-urology, especially in the context of urinary tract infections (UTI) and ante-natally diagnosed hydronephrosis, heavily relies on functional studies for patients’ management. In more recent years, other clinical subspecialties within paediatrics, such as oncology, orthopaedics, neurology/neurosurgery, have seen a growing interest in nuclear medicine imaging. Nuclear medicine imaging techniques provide a functional evaluation of paediatric pathology. The different radiopharmaceuticals used are taken up at cellular level and explore different aspects of cellular viability. These tests are essential in the diagnostic work up of many conditions, and, in some instances, in the evaluation of response to treatment. Paediatric nuclear medicine imaging calls for special skills by the radiographers/technicians, who acquire the examinations, and the nuclear medicine specialist, who issues a clinical report. The child is not a small adult and dealing with children and their families requires the ability to gain the children's and family's trust and cooperation, so that the child keeps still on the gamma camera couch during the images acquisition and, as a result, the examination can answer the clinical question. A detailed knowledge of the relevant paediatric clinical conditions and of the contribution of the other imaging techniques toward patient's management is also required. Highly sophisticated equipment is not needed for the majority of the commonly requested radioisotope examinations; a single-head gamma camera is often sufficient. Nowadays, however, dual-head scanners capable of performing single photon emission computed tomography (SPECT), sometimes associated with a low-dose computed tomography (CT) for improved anatomical localization and image fusion, are routinely available in a standard nuclear medicine department. In a district general hospital equipped with paediatric services these scanners are useful in a relatively small proportion of paediatric nuclear medicine imaging tests. Sedation or general anaesthesia (GA) are used only in a minority of tests, usually examinations that require a long time (for example, bone scintigraphy especially if supplemented by a SPECT/CT), or when it is critical to have the patient absolutely still (such as for a brain SPECT, or for SPECT/CT studies in children with cancer). The age group when sedation or GA may be necessary is typically between 1 and 4–5 years. Co-existing pathologies such as autism or cerebral palsy may require the use of sedation or GA necessary also in older children. It is important that the referring clinical team liaises effectively with the nuclear medicine department so that the anaesthetists or the sedation nurse can be alerted well in advance if GA or sedation is needed. The referring clinician and the nuclear medicine specialist responsible for the examination should be mindful to keep the radiation dose delivered to the child as low as reasonably possible (ALARP). The majority of nuclear medicine imaging studies performed in children gives a low effective dose equivalent (EDE), well below 1 milliSievert (mSv). This is a small radiation dose, considering that the dose received by the general population due to the annual radiation background in the United Kingdom is ~2.7 mSv. Some gamma camera examinations, especially in oncology, neurology and orthopaedics, can give an intermediate radiation dose, between 3 and 6 mSv. Nuclear medicine imaging tests involving the use of positron emitting radioisotopes, may give a higher EDE. These tests are usually performed using a positron emission tomography (PET) scanner; the nuclear medicine component of the test is acquired in conjunction with a low-dose CT scan for attenuation correction and anatomical co-localization. The total EDE of the test, which includes the radiation burden from both the radiopharmaceutical and the CT component of the study, is in the range of 8–12 mSv. A combined effort is on-going around the world to harmonize the existing different approaches to calculate the radioactivity administered to the child into one single dose reduction protocol.1 This short review covers common indications and use of nuclear medicine imaging techniques in some major paediatric clinical conditions and aims to show how they integrate with other imaging techniques in guiding clinical management. Nephro-urology Nuclear medicine imaging techniques in paediatric nephro-urology are well established. They inform the clinical team on regional renal parenchymal function, estimate the contribution of each kidney to the total glomerular filtration rate (GFR), and, in the case of the radionuclide dynamic renography, assess drainage, showing if there is urinary stasis and where is it (in the renal pelvis or ureter, or at both sites). The calculation of the split renal parenchymal function has been validated2 and comprehensive guidelines on the acquisition, processing and interpretation of these studies have been published.3–6 Radiopharmaceuticals The most commonly used radiopharmaceuticals in paediatric nephro-urology are Tc-99m-dimercaptosuccinic acid (DMSA) and Tc-99m-mercapto-acetyl-triglycine (MAG3). A Tc-99m-DMSA static scintigraphy is the current gold standard examination to assess the integrity of the renal parenchyma and the contribution of each kidney to the total renal parenchymal function, and is highly sensitive in the identification of cortical renal scars. This radiopharmaceutical is slowly taken up by the proximal renal tubules. Imaging is usually acquired between 2 and 4 h after tracer injection. Only a relatively small proportion of radiopharmaceutical is excreted via the urinary system, the remainder remains within the cells of the proximal renal tubules in the renal parenchyma. The EDE administered by a DMSA scan is low, varying between 0.6 and 0.8 mSv. A Tc-99m-MAG3 dynamic renography informs on renal perfusion, renal parenchymal function and drainage from the renal collecting system and ureters. Similarly to Tc-99m-DMSA, Tc-99m-MAG3 is taken up by the proximal renal tubules. However, unlike Tc-99m-DMSA, Tc-99m-MAG3 does not stay in the proximal renal parenchymal tubules but is excreted into the tubular lumen, thus reaching the renal collecting system and bladder via both ureters. The patient lies supine on the gamma camera couch for a dynamic acquisition which usually lasts between 20 and 30 min. The EDE from a MAG3 renogram is low, in the range of 0.3–0.7 mSv. In the vast majority of cases, the split renal parenchymal function evaluation given by the MAG3 renogram is reliable; therefore an additional DMSA scan with the only purpose of assessing split renal function is not required. Exceptions include a grossly enlarged kidney, or conditions with poor parenchymal extraction of the radiopharmaceutical, with high background activity, such as very immature kidneys or severe chronic kidney disease. Urinary tract infections and vesico-ureteric reflux Primary goal in the diagnosis of a UTI is to reduce the incidence of recurrent UTI and prevent acquired renal parenchymal damage. The purpose of imaging is to detect pathological malformations and/or risk factors that, if not diagnosed and managed appropriately, might lead to additional infections and parenchymal damage. Vesico-ureteric reflux (VUR) refers to the retrograde flow of urine from the bladder into the ureter and, usually, into the renal collecting system. The clinical importance of VUR consists in its association with pyelonephritis and its contribution to reflux-related renal scarring. Not all types of VUR carry the same risk of renal scarring, with high-grade VUR being associated with a higher risk of renal scarring and recurrent UTIs, while lower grade VUR carries a lower risk of renal scarring.7 Imaging tests in a child with UTI and VUR The ultrasound examination, the micturating cystourography (MCUG) and the Tc-99m-DMSA static renal scintigraphy are the core imaging tests utilized in children with UTI at risk of developing renal parenchymal damage. A renal ultrasound examination can define the kidney shape, length, echogenicity and the presence of pelvi-calyceal and ureteric dilatation. Ultrasonography can also describe bladder volume, bladder wall thickness, possible renal and bladder calculi, ureteric abnormalities and adjacent pathology (such as collections). The disadvantages are the poor detection rate of parenchymal defects and vesico-ureteric reflux (VUR). The MCUG is the most widely used radiological examination for the study of the lower urinary tract and especially of VUR. MCUG should always be performed in infant boys at risk of VUR, to exclude posterior urethral valves. The disadvantage of this test is the placement of a bladder catheter, which is unpleasant especially in grown up children. A Tc-99m-DMSA static renal scintigraphy can be used acutely during or shortly after the UTI, to confirm the presence of acute pyelonephritis, or 4–6 months after the UTI, to look for renal scarring. An acute DMSA scan may show reduced tracer uptake in areas of acute inflammation, probably reflecting both focal tubular cell dysfunction and ischaemia.8 This test can confirm the diagnosis of acute pyelonephritis, especially in patients with equivocal symptoms.9 The sensitivity of Tc-99m-DMSA scintigraphy for the early diagnosis and localization of acute pyelonephritis reaches over 90%.10 The advantage of this approach is that in patients with normal acute DMSA the likelihood of developing renal scarring is almost zero.11 If treated appropriately within 48 h, acute pyelonephritis may resolve completely and scintigraphic images typically become normal within 4–6 months. Alternatively, without adequate and early antibiotic treatment, a permanent cortical scar may develop. A mature cortical scar is usually associated with contraction and apparent loss of volume of the involved cortex. On ultrasonography, this may manifest as cortical thinning, flattening of the renal contour, or a wedge-shaped defect. The scintigraphic pattern of a maturing scar on DMSA varies according to the severity of the UTI, the location of the lesion, the age of the patient, as well as the rate of growth of the surrounding normal renal tissue. A DMSA scan should be performed 4–6 months after a UTI if the clinical question regards the presence of focal renal scarring (National Institute for Health and Clinical Excellence, NICE) (Fig. 1). Knowledge of the degree of scarring after an infection is important because patients with severely scarred kidneys are at higher risk of hypertension and chronic kidney disease, while a small scar is likely to be clinically insignificant.12,13 Fig. 1 Open in new tabDownload slide (a, b) DMSA scan on a 7 year old girl with a history of recurrent urinary tract infections, bladder dysfunction and left sided vesico-ureteric reflux. The left kidney shows globally reduced tracer uptake with multiple renal scars. The right kidney is normal. The left kidney contributes 26% to total renal function, right kidney 74% (a). Four years later (b) the left kidney has further deteriorated, with more extensive scarring and a slight reduction in renal function (from 26% to 14% contribution to total GFR, with the right kidney contributing 86%). Fig. 1 Open in new tabDownload slide (a, b) DMSA scan on a 7 year old girl with a history of recurrent urinary tract infections, bladder dysfunction and left sided vesico-ureteric reflux. The left kidney shows globally reduced tracer uptake with multiple renal scars. The right kidney is normal. The left kidney contributes 26% to total renal function, right kidney 74% (a). Four years later (b) the left kidney has further deteriorated, with more extensive scarring and a slight reduction in renal function (from 26% to 14% contribution to total GFR, with the right kidney contributing 86%). Nuclear medicine imaging can demonstrate the presence of VUR. In toilet trained and cooperative children (usually above 3 years of age) a sequence of images can be acquired at the end of the MAG3 renogram, when the bladder is filled with tracer and the child wants to void (indirect radionuclide cystogram). This approach has the advantage of a completely physiological evaluation of micturition and does not need a bladder catheter. The timing and completeness of bladder emptying can also be evaluated, thus giving some insights on bladder function. The disadvantage is the suboptimal anatomical definition of the renal excretory system. The indirect radionuclide cystogram is the first line examination to look for VUR in toilet trained children. In non-toilet trained children, a bladder catheter is inserted and a small amount of radioactive tracer (usually Tc-99m-pertechnetate) instilled in the bladder together with saline (direct isotope cystography, DIC). Dynamic imaging is then acquired. This approach is very sensitive in detecting VUR and gives an extremely low EDE (0.01 mSv). It tends to be used in children, especially girls, in follow up for VUR. The disadvantage is that the anatomical definition is poor. Currently, the new fluoroscopic units administer a very low radiation dose while providing at the same time a detailed definition of the anatomy of the renal excretory system; as a result, the DIC is losing favour. Children on clean intermittent catherization (CIC) for neuropathic bladder are used to the insertion of bladder catheters and find it easier to cooperate for a radiological MCUG, which gives the advantage of a much better anatomical detail. Imaging strategies in a child with UTI The use of diagnostic imaging tests in a child with UTI is still a matter of controversy. In much of the literature considerable attention has been placed on the diagnosis of VUR. Because the presence and the severity of VUR can be reliably determined only by MCUG, some groups have advocated performing MCUG in all children after a first febrile UTI.14 Alternatively, the so-called ‘top down’ approach is adopted in many countries. This imaging strategy aims to reduce the number of MCUGs. A DMSA scan is performed during the acute phase of the UTI. If this is positive, the chance of dilating VUR is high and a MCUG will be performed. If the acute DMSA is negative, a MCUG is not performed.15–17 In 2007 the National Institute for Health and Clinical Excellence (NICE) published a set of guidelines on UTIs (revised in 2015).18 The main philosophy of these guidelines is to concentrate imaging studies in the child clinically at risk of developing renal damage following an episode of infection. Children with a non-febrile UTI do not need any initial imaging of their urinary tract. Children with recurrent attacks of lower UTI might need imaging that focuses on bladder function. Children with febrile UTI can be divided into two groups: children at high risk and at low risk of developing renal damage. If the UTI is atypical or they have recurrent UTI, the children fall in the high risk category and need an ultrasound examination at 6 weeks and a DMSA scan at 4–6 months after the UTI. High-risk children under 6 months of age require a renal tract ultrasound examination during the acute infection followed by a DMSA 4–6 months after the UTI and a MCUG. Children between 6 months and 3 years of age do not require any imaging if they respond to antibiotic treatment within 48 h and are classified as low risk. Low risk children need no imaging if they do not develop a second UTI (which brings them into the high risk group). The NICE guidelines have been criticized by studies that show that a significant number of abnormalities, especially high-grade VUR, may be missed if the guidelines are followed.19,20 In conclusion, controversy still exists on imaging and management of UTI. Long-term cohort studies with sufficient statistical power that establish the prognostic significance of renal scarring are needed. Ante-natally diagnosed hydronephrosis Renal pelvic dilatation Multiple conditions can cause renal pelvis dilatation, such as pelvi-ureteric junction (PUJ) anomaly, VUR, posterior urethral valves, vesico-ureteric junction (VUJ) anomaly, and a duplex kidney with a dilated renal pelvis. Renal ultrasonography is usually the first imaging test in this clinical setting. This informs on kidney size, degree of cortico-medullary differentiation, morphology of the renal parenchyma, the size of the renal pelvis and calyces, the possible presence of ureteric dilatation, the size of the bladder and wall thickness. In the case of a PUJ anomaly, the ultrasound examination shows a dilated renal pelvis with no evidence of ureteric dilatation, and a MAG3 renogram shows urinary stasis at the level of the PUJ (Fig. 2). A PUJ anomaly should particularly be suspected when moderate (10–15 mm) or severe (>15 mm) dilation is seen.21 Fig. 2 Open in new tabDownload slide Open in new tabDownload slide (a, b) MAG3 renogram on a 3 months old baby boy, with an ante-natally diagnosed severe right hydronephrosis. The dynamic renography (a) shows a tilted right kidney due to the very large extrarenal pelvis. Tracer uptake within the right renal parenchyma is slightly reduced. The right kidney contributes 40% to total renal function (left kidney 60%). There is very slow drainage from the right renal collecting system with hold up at the level of the PUJ. The post-micturition view demonstrates persistent urinary stasis in the right renal pelvis at the level of the PUJ. The time activity curve of the right kidney is rising, even more so when the post-micturition view is considered (b), in keeping with very poor drainage from the right kidney. The ultrasound did not show right ureteric dilatation. The appearances are consistent with a right PUJ anomaly. The left kidney is normal. The child had a right pyeloplasty. Fig. 2 Open in new tabDownload slide Open in new tabDownload slide (a, b) MAG3 renogram on a 3 months old baby boy, with an ante-natally diagnosed severe right hydronephrosis. The dynamic renography (a) shows a tilted right kidney due to the very large extrarenal pelvis. Tracer uptake within the right renal parenchyma is slightly reduced. The right kidney contributes 40% to total renal function (left kidney 60%). There is very slow drainage from the right renal collecting system with hold up at the level of the PUJ. The post-micturition view demonstrates persistent urinary stasis in the right renal pelvis at the level of the PUJ. The time activity curve of the right kidney is rising, even more so when the post-micturition view is considered (b), in keeping with very poor drainage from the right kidney. The ultrasound did not show right ureteric dilatation. The appearances are consistent with a right PUJ anomaly. The left kidney is normal. The child had a right pyeloplasty. It has been noted that the vast majority of PUJ anomalies resolve spontaneously. Only in ~25–30% of cases a PUJ anomaly causes a significant resistance to urinary outflow, with backward pressure on the renal tubules. This results in a stretched renal parenchyma and, in the long term, loss of renal parenchymal function if the condition is left untreated.22 The diagnostic challenge is to identify early on the subgroup of children at risk of losing renal parenchymal function and treat them aggressively, while the others can be monitored and subsequently discharged. Preliminary work, which needs further evaluation, has shown that prolonged transit of tracer through the renal parenchyma of the hydronephrotic kidney, in comparison to the normal contralateral kidney, may be a valuable parameter to identify the kidney at risk.23 Therefore, not all children with a PUJ anomaly need nuclear medicine imaging. This is reserved for children with a moderately to much dilated renal pelvis (>12 mm in AP diameter) and with calyceal dilatation.24 When functional imaging is indicated, a dynamic radionuclide renography with Tc-99m-MAG3 is the test usually requested. It informs the referring clinician on the contribution of the hydronephrotic kidney to total renal parenchymal function and the possible presence of focal areas of reduced or absent parenchymal function. It also informs on the site of urinary stasis, for example whether this is at the level of the PUJ or VUJ. A renal scintigraphy can be performed in an infant as young as 6 weeks of age. It is important to be aware that slow drainage on a MAG3 renogram in an asymptomatic child with an ante-natally diagnosed hydronephrosis does not necessarily mean obstruction.25 Slow drainage can be due to pooling of tracer in a dilated renal pelvis, with subsequent drainage following change of position and micturition. It could also be due to a PUJ or VUJ stenosis that is not tight enough to cause significant resistant to urinary outflow and consequent loss of renal parenchymal function. In this condition the pelvi-calyceal system is in equilibrium.26 A PUJ obstruction is usually diagnosed in the presence of symptoms (colic pain, UTI), increased renal pelvic dilatation on ultrasonography, or significant reduction in renal parenchymal function on radionuclide renography. The criteria for surgery are still not well-defined and vary between institutions. A renal pelvic dilatation larger than 3 cm, the presence of calyceal dilatation, reduced renal parenchymal function, have been included as surgical criteria.27 The recommendation is to perform an open, laparoscopic or robotic assisted pyeloplasty, according to the standardized technique of Anderson and Hynes. Nuclear medicine imaging with Tc-99m-MAG3 will show the degree of renal parenchymal function and whether there is hold up of tracer at the level of the PUJ or the VUJ. Obviously, if the patient is symptomatic with colic pain or UTI he/she will be referred promptly for treatment. A Tc-99m-MAG3 dynamic renography can be very helpful in assessing the outcome after surgery, and is usually performed not earlier than 6–9 months post-operatively, to allow the post-surgical oedema and stiffness of the tissues to settle. A change in split renal parenchymal function of <5% between two serial MAG3 renograms is unlikely to be significant. A change between 5% and 10% may or may not be significant. If the baseline scan was acquired in a very young child, younger than 6 months of age, and with immature kidneys with reduced tracer uptake and raised background activity, or in a child with chronic kidney disease, then the estimation of the split renal function was probably not very precise, and this will have to be taken into account when comparing the following MAG3 renogram. In this case, a difference in split renal function of up to 10% may not be significant. Megaureters A dilated ureter, or megaureter, may be dysplastic and flaccid, with loss of peristalsis, or may develop as the result of a stenosis at the level of the VUJ (VUJ anomaly). It can be obstructing, refluxing, non-obstructing and non-refluxing. The renal ultrasound examination will show the calibre of the dilated ureter both proximally and distally and the size of the renal pelvis, which is often dilated. A megaureter may present with UTI or may be detected on an ante-natal ultrasound examination and followed up post-natally. Nuclear medicine imaging informs the referring clinician on the parenchymal function of the hydro-ureteronephrotic kidney and shows if there is urinary stasis at the distal end of the dilated ureter. Sometimes the nuclear medicine study shows urinary stasis in the renal pelvis, with little or no stasis in the dilated ureter; if the ultrasound examination shows a significantly dilated ureter, then a VUJ anomaly is still possible and further evaluation with cystoscopy and a retrograde radiological contrast study, with the view of proceeding to incisor balloon dilatation of the VUJ orifice, may be required. An anomaly at both the PUJ and the VUJ levels may coexist. It is difficult to diagnose this association with a nuclear medicine study; an ultrasound examination is always necessary to demonstrate the size of the renal pelvis and ureter; a radiological contrast study, performed either retro-gradely via cystoscopy or ante-gradely, with percutaneous puncture of the renal pelvis, sometimes may also be required. Other congenital renal anomalies Duplex kidneys Nuclear medicine imaging techniques successfully assess renal parenchymal function and drainage in patients with congenital renal anomalies. In a kidney with a duplex renal collecting system, a MAG3 renogram can confirm the diagnosis and show whether the renal parenchyma of the upper and the lower moieties is functional. The upper moiety of a duplex may be obstructed at the distal end by an ureterocele and, as a result, may drain slowly via a dilated and tortuous ureter. The functional radioisotope study is essential to show the degree of renal parenchymal function. A poorly functional (or non-functional) upper moiety of a duplex kidney is usually managed surgically with an upper pole heminephrectomy. The lower moiety of a duplex kidney may show VUR, due to the abnormal entry of the lower moiety ureter into the bladder. In a child with recurrent UTIs, if the nuclear medicine study (Tc-99m-DMSA scintigraphy or Tc-99m-MAG3 dynamic renography) shows significant residual parenchymal function in the lower moiety, the VUR may be treated endoscopically with a deflux procedure. If the lower moiety shows very poor or absent parenchymal function, the treatment of choice will be a lower pole heminephrectomy. Fused kidneys Nuclear medicine imaging is important to confirm the presence of fused kidneys, which can be difficult to demonstrate on the ultrasound examination due to the presence of bowel gas; it can also show the presence of possible renal cortical scars. Horseshoe kidneys are usually fused at the lower pole and positioned low in the abdomen. Due to their unusual position and the abnormal orientation of their collecting systems, urinary stasis is possible, and one or both moieties may become hydronephrotic. A nuclear medicine imaging study, either a Tc-99m-DMSA scintigraphy or a Tc-99m-MAG3 dynamic renography, can confirm the diagnosis, show the possible presence of renal scars and, in the case of a MAG3 renogram, if there is urinary stasis in the renal collecting system. Nuclear medicine imaging provides useful information in crossed-fused renal ectopias. A Tc-99m-DMSA study is usually preferred to inform on renal parenchymal integrity and on the possible presence of focal renal scars. The study can be supplemented by a SPECT/CT acquisition, to view the data in three dimensions this improving anatomical definition. In the case of a multicystic dysplastic kidney (MCDK) a DMSA will confirm the diagnosis, suggested already by the ultrasound examination. There will be no renal parenchymal function in the MCDK. The study will also inform on the parenchymal function of the contralateral kidney. Hypertension In the hypertensive child a DMSA scan is important to rule out multiple renal scars as a possible cause of hypertension. In the case of renovascular hypertension, due for example to fibro-muscular dysplasia, neurofibromatosis 1, mid aortic syndrome or extrinsic compression on the renal artery by an adjacent mass lesion, a DMSA scan will be helpful to assess renal parenchymal function before and after procedures such as angioplasty, surgical revascularization or resection of the mass lesion. Dynamic renal scintigraphy has been utilized in the diagnostic work up of renovascular hypertension, especially before and after administration of an angiotensin-converting enzyme (ACE) inhibitor such as captopril.28 This technique is weak in bilateral or segmental disease and its use in the diagnostic algorithm of renovascular hypertension is no longer routinely advocated.29 Renal vein thrombosis Dehydrated neonates and those with a traumatic delivery can develop renal vein thrombosis. In these infants, a DMSA scan performed 3–6 months after birth will show the parenchymal function of the kidneys. Renal vein thrombosis may affect one or both kidneys at varying degree, depending on the degree of venous obstruction. Oncology Molecular imaging techniques are increasingly utilized in paediatric oncology. The main questions asked by the referring clinical team are the demonstration of regional or distant metastases, thus contributing to staging the disease, the identification of an appropriate site for biopsy, the evaluation of response to treatment, the differentiation between residual disease and post-therapy changes, the identification of possible recurrent disease. It is critical to acquire images of the highest possible quality, as the demonstration of a small but definite focus of disease can at times change management significantly. Therefore, the child has to be absolutely still during the acquisition of the images. Sedation or GA is often needed in young children. It is important that the referrer assesses the patient to see whether he/she will be able to cooperate for the study or whether sedation or GA will be needed, and inform the nuclear medicine team. The patient may have to be seen by the anaesthetic team or sedation nurse to make sure that he/she is suitable for sedation/GA. Radiopharmaceuticals Gamma camera radiopharmaceuticals Meta-iodo-benzyl-guanidine (mIBG) labelled with either I-123 or I-131 has been clinically available for the last 30 years. MIBG is an analogue of norepinephrine and is internalized in the pre-synaptic cells of the sympathetic nerve fibres.30 I-131 labelling is suboptimal for gamma camera imaging, due to its unfavourable physical properties, and its use has been discouraged.31 I-123 labelling is much better suited for gamma camera imaging. I-123-mIBG is a cornerstone examination in the management of neuroblastic tumours. Some medications (such as labetolol and some decongestant drugs) interfere with its uptake and should be withdrawn prior to tracer injection for a variable time up to 1 week. The EDE from an I-123-mIBG scan is intermediate, in the range of 5–7 mSv, depending on the patient's age. State-of-the-art mIBG imaging includes planar images with a SPECT acquisition, often supplemented by a limited low-dose CT for anatomical localization. The radiation dose from the CT component of the study is often well below 1 mSv, if child-friendly CT protocols are used. Tc-99m-methylen-diphosphonate (MDP) or HDP is used to perform bone scintigraphy. The distribution of Tc-99m-MDP depends on blood flow and bone turnover. Tracer uptake is related to osteoblastic activity. The EDE given by a bone scintigraphy in a child varies between 3.5 and 5.5 mSv, according to age. Positron emission tomography radiopharmaceuticals PET is gradually been introduced as a molecular imaging modality in paediatric oncology. A PET study is usually supplemented by a low-dose CT scan for attenuation correction and anatomical localization. Fluoro-18-fluorodeoxyglucose (FDG), a positron emitter that reflects tumour glucose metabolism, is the main radiotracer currently used. FDG is taken up through a transmembrane glucose transporter but does not enter the energy producing metabolic pathways. Tracer uptake correlates with glucose metabolism. The EDE from a FDG PET scan is intermediate to high, ranging between 6 and 8 mSv. The added radiation dose from the CT component of the study is in the order of 2 mSv. Several other PET tracers, such as somatostatin analogues (Ga-68-DOTA peptides) and F-18-fluoro-dihydroxyphenylalanine (FDOPA) are under evaluation and are likely to be more widely used soon. Lymphoma FDG PET/CT scanning in paediatric Hodgkin's lymphoma (HL) is used to stage the disease and to evaluate response to chemotherapy. FDG PET/CT has proved to be more sensitive than CT in the evaluation of some sites of disease.32 In particular, FDG PET/CT can demonstrate tumour involvement in normal sized lymph nodes on CT; it can also show spleen, liver and bone marrow involvement. The sensitivity of FDG PET/CT for lung disease is limited, as the CT component of the study is acquired with the patient on shallow breathing. A dedicated fully diagnostic CT chest is required to demonstrate lung disease. Evaluation of response to chemotherapy in HL can be performed during therapy (interim FDG PET scan) or at the end of therapy. In the adult practice recent studies have shown that a patient with early resolution of disease during chemotherapy has a better prognosis,33 and radiotherapy at the sites of the original disease is not indicated.34 On the other hand, a patient with residual FDG avidity after completion of chemotherapy, if confirmed as malignant at biopsy, will have a less favourable outcome.35,36 Whole body (WB) MRI could potentially be an alternative to FDG PET/CT at staging in HL, but further work is necessary. It has been shown to be equal to FDG PET/CT in ~75% of cases, while in the other cases it has led to over staging in comparison to the findings on FDG PET/CT, with clinically relevant results in 10% cases.37 Other studies have shown very good interobserver agreement between WB MRI and FDG PET/CT for both nodal and extranodal sites.38,39 With regard to paediatric non-Hodgkin's lymphomas, the role of FDG PET/CT is yet to be determined. A negative FDG PET/CT study in the evaluation of residual disease is likely to be a good indicator of complete remission; false positive FDG findings are common and biopsy and close monitoring are necessary.40 Neuroblastoma The majority of patients with neuroblastoma present with distant metastases (Stage IV or M). Neuroblastoma tends to metastasize predominantly to the skeleton (cortical bone and bone marrow); other sites of metastatic disease include regional and distant lymph nodes, and, less frequently, liver, skin, brain and lung. I-123-mIBG has high sensitivity and specificity for neuroblastoma; in addition, mIBG positive neuroblastomas can be treated with I-131-mIBG molecular radiotherapy. I-123-mIBG is used in neuroblastoma staging. The bulk of mIBG avid metastatic skeletal disease at diagnosis has prognostic value: the presence of more than three sites of mIBG avid metastatic skeletal disease is associated with a poorer prognosis in comparison to less than three sites (Fig. 3). This tracer is also valuable in the evaluation of response to chemo- and radiotherapy. The bulk of residual disease following chemotherapy has prognostic significance.41 Fig. 3 Open in new tabDownload slide Four year old girl with a right suprarenal mass lesion, raised urinary catecholamines and a diagnosis of poorly differentiated neuroblastoma on biopsy. The I-123-mIBG scan at staging (planar images) shows avid tracer uptake within the primary tumour in the left suprarenal region and widespread skeletal metastatic infiltration. The patient was treated with an aggressive chemotherapy regimen and achieved complete remission of the metastatic deposits. The primary neuroblastoma was completely excised. Fig. 3 Open in new tabDownload slide Four year old girl with a right suprarenal mass lesion, raised urinary catecholamines and a diagnosis of poorly differentiated neuroblastoma on biopsy. The I-123-mIBG scan at staging (planar images) shows avid tracer uptake within the primary tumour in the left suprarenal region and widespread skeletal metastatic infiltration. The patient was treated with an aggressive chemotherapy regimen and achieved complete remission of the metastatic deposits. The primary neuroblastoma was completely excised. Approximately 10% of neuroblastomas are mIBG negative at diagnosis. FDG PET/CT has been used in these patients, with mixed results.42–44 Therefore, the use of other PET tracers is being evaluated, such as somatostatin analogues (Ga-68-DOTA peptides) and F-18-deoxy-phenyl-alanine (F-DOPA).45,46 Bone scintigraphy has currently no role to play in children with neuroblastoma. It fails to identify bone marrow disease, very frequent in neuroblastoma. Cortical bone metastases can be visualized; however, as skeletal uptake of the bone scan tracer reflects an on-going osteoblastic activity, abnormal cortical uptake may persist as a false positive finding even when the metastatic lesions have resolved. Brain tumours Imaging of the central nervous system (CNS) tumours is mainly based on magnetic resonance imaging (MRI) as the cornerstone imaging modality. Although MRI provides good sensitivity and specificity, this technique presents some pitfalls. The borders of tumour mass not always coincide with the MRI findings. Some brain tumours tend to have a heterogeneous cell population, with highly malignant cells alternating to cells with less pronounced cellular atypias. A significant problem often encountered in the evaluation of response to surgery and radiotherapy is the difficulty in distinguishing between recurrent tumour and post-radiotherapy fibrosis.47 Similarly, identification of new effective drugs relies on the assessment of an objective response demonstrated on imaging. This assumes that changes seen on imaging represent the biological activity of the tumour itself. However, this is not always the case. Molecular imaging in CNS tumours with PET can be used to analyse physiologic and metabolic changes in healthy and pathologic tissue, monitoring treatment effect and detection of recurrence.48 FDG is not an ideal tracer for brain tumours, due to the physiological high uptake within the normal brain. However, high-grade brain tumours show highly increased FDG uptake, often higher than the normal brain. In these tumours FDG PET, especially if co-registered with MRI, can be helpful in differentiating tissue necrosis following radiotherapy from recurrence. FDG uptake is a predictor of prognosis and is particularly useful for distinction of brain lymphoma from non-malignant lesions.49 Amino acid tracers are promising in that they are avidly taken up by tumours and show low uptake in normal brain tissue. The best studied amino acid tracer is C-11-methionine. Because of the short half-life of C-11 (20 min), F-18-labelled aromatic amino acids have been developed for tumour imaging. Tumour uptake of F-18-fluoro-ethyl-l-tyrosine (FET) and 3,4-dihydroxy-6-F-18-fluoro-l-phenyl-alanine (FDOPA) has been reported to be similar to C-11-methionine.50 The distinction between radiotherapy induced necrosis and recurrent tumour is a persistent challenge in the management of brain tumours. All available tracers have demonstrated potential to assist with this distinction but the results from various studies show considerable variation in sensitivity and specificity.51–53 In particular, amino acid tracers appear to be particularly useful for detection of recurrent tumours,54–56 but their availability is limited as yet. PET imaging techniques are also increasingly being used to improve the accuracy of histologic diagnosis by targeted biopsies and for radiotherapy planning.57–59 Other paediatric malignancies Rhabdomyosarcoma (RMS) is the commonest soft tissue sarcoma (STS) in children and represents 7% of all children's cancers. Around 40% of RMS arise in the head and neck, 20–25% in the pelvis and 25–30% in the trunk and limbs. The histology of RMS varies, with two main subtypes alveolar and embryonal found in children. The primary tumour is usually best imaged by MRI, including draining lymph nodes. CT of the chest, bone scintigraphy and bone marrow aspirate and trephine biopsy are routine part of the staging. The use of FDG PET/CT in paediatric sarcoma is still under scrutiny but it appears useful in evaluating nodal and metastatic disease.60–63 Osteosarcoma accounts for 2.5% of all paediatric malignancies under the age of 15 years, as the peak age coincides with a period of rapid bone growth at the time of puberty. Imaging tests at diagnosis include plain radiographs and MRI of the primary tumour, CT of the primary tumour and lungs (frequent site of metastases), bone scintigraphy to show metastatic bone disease. Ewing's sarcoma classically occurs in the second decade of life, affecting fewer than three in every 1 million children under 15 years of age. Plain radiographs may reveal the moth-eaten bone with raised periosteum. MRI defines the extent of soft tissue involvement. Metastatic disease should be sought in the lungs (chest CT), bones (bone scan) and bone marrow (aspirates). Recent reports suggest that FDG PET/CT may be more sensitive than bone scan for skeletal disease.64 Inflammation and infection Infection, connective tissue disease and neoplasm are the most common causes of FUO; a cause for it cannot be established in ~20% of them. FDG PET/CT can also be used in patients with fever of unknown origin (FUO) and has replaced Gallium-67, which gives an unacceptably high radiation burden.65,66 Nuclear medicine imaging can be helpful in immuno-compromised patients to identify the site of an infective focus in the context of opportunistic infections.67 FDG PET can differentiate between toxoplasmosis and lymphoma in the central nervous system.68 FDG PET/CT has been shown to be promising in patients with large vessel vasculitis such as Takayasu disease; in patients with medium and small vessel disease, however, the resolution of PET is inadequate to identify disease activity, unless there is involvement of the adjacent soft tissues.69–71 FDG PET/CT is not reliable if the patient is on steroids.70 In inflammatory bowel disease (IBD) the Tc-99m-labelled white cell scan has been used to differentiate between active inflammation, which may respond to medical therapy, and scarring, which may require surgery.72 However, in recent years this test has been largely superseded by MR enterography, which has the great advantage of a much simpler execution of the test and the lack of ionizing radiation.73 MR enterography provides excellent bowel detail, allows the study of acute and chronic bowel wall inflammation, its early and late complications, the presence of extra-intestinal disease and incidental findings, and should be the primary cross-sectional imaging modality in children evaluated for IBD. Musculo-skeletal applications Bone scintigraphy with Tc-99m-labelled diphosphonates has been successfully used in musculo-skeletal (MSK) conditions for many years. Bone scintigraphy in children can be performed in the following conditions: osteomyelitis, chronic recurrent multifocal osteomyelitis (CRMO), inflammatory arthropathies, sports injuries, back pain, avulsion fractures, localization of the source of pain, non-accidental trauma, avascular necrosis of the bone, benign bone tumours, fibrous dysplasia, hyperostosis, oncological disorders (osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma with unfavourable prognosis). However, and especially in the presence of localizing symptoms and following an X-ray radiograph, MRI tends to be favoured as the first-choice investigation in some of these conditions. If MRI is not readily available or the child needs sedation or GA, and this is difficult to organize, bone scintigraphy is usually the next choice. Osteomyelitis is a common problem in paediatrics; it may be haematogenous or the result of penetrating trauma. When the spread of infection is haematogenous, the metaphysis of long bones is most likely to be involved owing to the slow blood flow, although flat bones may also be affected. In a suspected osteomyelitis with symptoms localizing to a particular skeletal segment, the first imaging test is a plain X-ray, usually followed by MRI. If a focus is identified, no further imaging is necessary. If there are no localizing symptoms, or MRI is not readily accessible, a three-phase bone scan is justified. High quality bone scanning is highly sensitive for osteomyelitis, with hyperaemia and highly increased tracer uptake demonstrated at the focus of infection. An accuracy of 92% has been reported for skeletal scintigraphy in osteomyelitis.74–76 The abnormality on bone scan is demonstrated within 24–48 h from the onset of symptoms, much earlier than on the plain radiograph. A SPECT/CT acquisition can add important anatomical detail by precisely localizing the abnormality, especially if a bone biopsy is contemplated. Bone scintigraphy can be helpful in inflammatory conditions such as juvenile rheumatoid arthritis, IBD, psoriasis and connective tissue disease such as systemic lupus erythematous, especially where access to MRI is more difficult. Bone scintigraphy is more sensitive than radiography and clinical examination for detecting inflammatory joint disease of wrists, hands, ankles and feet. In addition, a negative bone scintigraphy accurately excludes active arthritis in patients with persistent polyarthralgia.77 Skeletal scintigraphy with SPECT/CT is an increasingly important test in the identification of the source of MSK pain due to mechanical stress at cortical bone level. In these conditions MRI is often negative or equivocal, and a CT scan fails to differentiate between areas of sclerosis, due to an old inactive process, and on-going active mechanical stress. For example, in children and adolescents with back pain and no obvious cause for it on plain film or MRI, a bone scan with SPECT/CT can identify active facet joint disease which could benefit from steroid injection78 (Fig. 4). Also, recent spondylolysis with increased tracer uptake on bone scan could be managed with surgical fixation, while old spondylolysis with no tracer uptake needs bone grafting as well to facilitate union of the two ends of the fracture.79 Bone scanning with SPECT/CT can also be very helpful in localizing bone pain of the foot or hand in patients where clinical examination, plain radiograph and MRI have not convincingly identified the source of pain.80 Fig. 4 Open in new tabDownload slide (a-c) Sixteen years old girl with L5 bilateral spondylolysis treated with posterior instrumentation 7 years ago. Recurrent right sided low back pain. The planar images of the bone scintigraphy (a) show a focal area of mildly increased tracer uptake in the right side of L5; however, no precise anatomical localization is possible to guide further treatment. The SPECT/CT study (b, c) shows that the focal uptake localizes to the right facet joint between L5 and S1. This finding prompted steroid injection at this site. Fig. 4 Open in new tabDownload slide (a-c) Sixteen years old girl with L5 bilateral spondylolysis treated with posterior instrumentation 7 years ago. Recurrent right sided low back pain. The planar images of the bone scintigraphy (a) show a focal area of mildly increased tracer uptake in the right side of L5; however, no precise anatomical localization is possible to guide further treatment. The SPECT/CT study (b, c) shows that the focal uptake localizes to the right facet joint between L5 and S1. This finding prompted steroid injection at this site. Gastro-intestinal radionuclide imaging Motility studies Nuclear medicine can be successfully utilized in the evaluation of gastro-intestinal (GI) motility. Gastric emptying scintigraphy is sensitive, physiological, non-invasive and safe in patients presenting with symptoms suggestive of abnormal gastric emptying. An anatomical obstruction, due for example to intestinal malrotation, must be excluded with a radiological contrast study prior to the scintigraphic study. In infants and new-born children, gastric emptying is assessed scintigraphically using milk or formula radiolabelled with Tc-99m-sulphur colloid. In older children a radiolabelled solid meal based on eggs, cheese or other feed can be used. A normal range of gastric emptying for a radiolabelled standardized meal based on eggs has been defined in the adult practice, with 10% or less of the initial gastric content remaining in the stomach at 4 h after ingestion of the radiolabelled test meal in a normal individual.81 In the paediatric population, more work has to be done to define a normal range, taking into account the age of the child and the test feed used. The EDE given by a gastric emptying study in a child is between 0.4 and 0.6 mSv (very similar to a radionuclide renal study). Small bowel transit can be assessed with radioisotopes. The recently published guidelines of the European Association of Nuclear Medicine (EANM) recommend the use of Tc-99m-diethylene-triamine-pentacetic acid (DTPA) dissolved in water and ingested as a tracer. Static imaging up to 6 h is acquired; occasionally, a repeat spot view at 24 h may be required to outline the colon. Normal small bowel transit has been defined in adults when at least 40% of the administered tracer has reached the ileo-caecal valve by 6 h.82 Colonic transit can be estimated with In-111-DTPA labelled water. This radiopharmaceutical is not absorbable in the gut. The patient is prepared with a bowel wash out to make sure that there are no impacted faeces in the colon. Medications that affect colonic transit are withdrawn (unless the purpose of the study is to assess the effectiveness of the medications). The study entails imaging of the abdomen and pelvis over up to 5 days. Imaging on the first day assesses gastric emptying and small bowel transit; at the end of the first day, activity in the colon is usually seen. Subsequently, static imaging is performed daily until the colon is empty or a clear pattern of colonic dysmotility has been demonstrated. If tracer is still seen in the colon by the end of the study, the patient undergoes a bowel wash out. This test can be used in children with severe constipation, unresponsive to medical treatment, to ascertain whether the problem is due to inertia of the whole colon or of a particular colonic segment, or else there is a functional outlet obstruction at the level of the recto-sigmoid.82 Gastro-intestinal bleeding A possible cause of gastro-intestinal bleeding in paediatrics is the presence of ectopic gastric mucosa within a Meckel's diverticulum. This is a congenital abnormality caused by incomplete closure of the embryonic omphalomesenteric duct. Bleeding from a Meckel's diverticulum is the result of peptic ulceration of ileal mucosa either in the diverticulum or in the adjacent ileum. The typical clinical presentation is with painless bright red per rectum bleeding. The tracer used is Tc-99m-pertechnetate, the injected activity is 1.85 MBq/kg. Premedication with proton pump inhibitors or H2-receptor antagonists is recommended by the EANM guidelines to prevent passage of tracer from the stomach where it is normally taken up, into the duodenum and jejunum.83 The scintigraphic test is performed by injecting Tc-99m-pertechnetate and acquiring a set of dynamic images of 1 min/frame over at least 30 min, followed by a set of delayed images after micturition. In the case of an equivocal finding, an acquisition with SPECT/CT can help clarify. Further delayed images may also help. If the test is performed according to the recommended guidelines the accuracy is around 90%, with a negative test reliably excluding ectopic gastric mucosa as the cause of the significant bleeding.84 Hepatobiliary imaging A possible indication for hepatobiliary scintigraphy in the neonate is the differentiation of biliary atresia from hepatocellular disease. Hepatobiliary scintigraphy with Tc-99m-mebrofenin can exclude biliary atresia if tracer is convincingly seen in the intestine. Phenobarbital, administered orally 3–5 days prior to tracer injection at the dose of 5 mg/kg/day, increases the extraction of tracer from the hepatocytes, thus increasing the sensitivity of the test. Deoxyursocholic acid can also be administered as an alternative.85 The scintigraphic diagnosis of biliary atresia is made when no tracer is excreted in the bowel and there is good tracer uptake in the liver parenchyma. Studies are interpreted as compatible with hepatocellular damage when there is reduced tracer uptake in the liver parenchyma, with slow transit of tracer through the biliary tree and some tracer eventually reaching the intestine.86 The definite diagnosis of biliary atresia requires percutaneous or intraoperative transhepatic cholangiography. Hepatobiliary scintigraphy can be repeated after a few days in the jaundiced new-born if the first examination does not demonstrate excretion of tracer in the bowel. Brain radionuclide imaging Epilepsy In ~30% of children with epilepsy, medical treatment fails to gain seizure control and surgery becomes the only option available to reduce seizure frequency and sometimes render the child seizure free. In ~50% of patients with drug resistant epilepsy, MRI either fails to clearly demonstrate the seizure focus, or is not concordant with the EEG findings.87,88 In this group of patients, nuclear medicine can be helpful. Nuclear medicine imaging techniques in drug resistant paediatric epilepsy are part of the diagnostic services usually available in centres that run an epilepsy surgical programme, and as such are highly specialized. These tests should not be performed in peripheral centres, and should not be interpreted in isolation from the other diagnostic tests. Ictal and interictal brain SPECT studies with regional cerebral blood flow tracers (Tc-99m-hexamethylpropylenamineoxime—HMPAO—and Tc-99m-ethylcysteinate dimer—ECD) can help identify the seizure focus in specific circumstances. In order to obtain a successful ictal study, tracer injection has to be administered during the actual seizure itself. The injection is usually given at seizure onset on the telemetry ward. The characteristics of the seizure will have to be known already from previous telemetry examinations. If the epileptogenic focus still discharges when the tracer reaches the brain, there is a good chance to identify the focus as an area of increased tracer uptake. In a normal resting condition, when the interictal scan is acquired, the epileptogenic focus will show either reduced uptake or a level of uptake similar to the surrounding cerebral tissue. The interictal scan can be subtracted from the ictal scan and the resulting map co-registered with the MRI to see more clearly the site of abnormal brain activity.89 An epileptogenic focus can be identified as a hypometabolic area with an interictal FDG PET/CT scan. The PET scan can be co-registered with the MRI for better anatomical localization. It is important to bear in mind that the area of hypometabolism demonstrated on PET can be larger than the actual epileptogenic focus itself. This is due to the cerebral damage caused around the focus, especially if the epilepsy has been long standing.87,88 Thyroid Congenital hypothyroidism The incidence is 1 in 4 000 new-born infants. The primary form of congenital hypothyroidism can be due to agenesis of the thyroid gland, a dysgenetic gland or dyshormonogenesis. Failure of descent of the thyroid to its physiological location in the neck during embryogenesis can lead to ectopic glands that are also usually dysgenetic. The much rarer secondary form of disease is due to thyroid stimulating hormone (TSH) deficiency, either isolated or due to pituitary hypoplasia, which may be associated to other pituitary hormone deficiencies. This condition is usually detected on neonatal screening. Investigations include a free thyroxine concentration (low) and a serum TSH (elevated). Thyroid scintigraphy with Tc-99m-pertechnetate is the most accurate test to locate the thyroid gland, differentiate between thyroid dysgenesis and dyshormonogenesis, and enable a decision to be made regarding life-long therapy (Fig. 5).90 In view of the association between congenital hypothyroidism and deafness, audiological assessment should be performed in these children. Fig. 5 Open in new tabDownload slide Neonate with raised TSH on screening test, confirmed on a venous blood sample, which also showed low free T4 (congenital hypothyroidism). Thyroid scintigraphy with Tc-99m-pertechnetate (lateral view), which shows a rudimentary lingual thyroid. Fig. 5 Open in new tabDownload slide Neonate with raised TSH on screening test, confirmed on a venous blood sample, which also showed low free T4 (congenital hypothyroidism). Thyroid scintigraphy with Tc-99m-pertechnetate (lateral view), which shows a rudimentary lingual thyroid. Transient hypothyroidism occurs in some children: this may be due to maternal antibody transmission, drugs or iodine imbalance. Hyperthyroidism Autoimmune thyrotoxicosis is six to eight times more common in girls. Thyroid stimulating antibodies are present in the serum of these patients and are responsible for the clinical picture. Autonomous functioning thyroid nodules are rare in children, as is autonomous TSH production from the thyrotrophs or pituitary tumours. Graves’ disease can occur in children, but there is a sharp increase in incidence in adolescence. Investigations of free thyroxine, free tri-iodothyronine and TSH concentrations (suppressed) are mandatory. A thyroid ultrasound examination may be required if a solitary nodule is suspected. The child is usually treated with anti-thyroid medications such as carbimazole or methimazole, with the possible additional use of propranolol to mitigate the cardiac symptoms. Graves’ disease may relapse once medication is stopped; remission rates are low in children, and may be <50% after 4 years. In the long term, definitive treatment in the form of a thyroidectomy or I-131 radioactive iodine may be indicated. Complications of surgery include hypoparathyroidism and recurrent laryngeal nerve damage. Radioiodine is easy to administer and cheap. To date, concerns about radiation oncogenesis and genetic damage has limited its use to adolescents, although anxieties regarding the former have largely been alleviated in adults. It is contraindicated in children with Graves’ eye disease. Thyroid cancer Thyroid nodules in young children have a higher likelihood of being malignant than in adults. Nuclear medicine has little role in the evaluation of a thyroid nodule in a euthyroid patient. These nodules are evaluated with an ultrasound examination and fine needle aspiration cytology. In a child or adolescent with thyroid cancer I-131 is used as a therapeutic option to ablate the thyroid following total thyroidectomy, and in the management of iodine avid relapse.91 Conclusion Paediatric nuclear medicine imaging is well-established in paediatric nephro-urology: it gives unique information on renal parenchymal function and drainage, thus complementing the other imaging modalities. In the context of UTI, the clinical significance of renal scarring in terms of subsequent risk of hypertension, chronic kidney disease and complications in pregnancy needs to be better evaluated. In the assessment of an ante-natally diagnosed hydronephrosis due to a PUJ anomaly, the identification of the hydronephrotic kidney at risk of losing parenchymal function if left untreated is an important research goal. PET tracers are increasingly utilized in paediatric oncology. The combination of PET and MRI imaging in one single scanner (PET/MRI) is very attractive in paediatrics: MRI is the cross-sectional imaging modality of choice in several paediatric malignancies with no ionizing radiations; PET offers a unique contribution to identify viable tumour tissue. Two complex examinations can thus be performed in one session. Bone scintigraphy with SPECT/CT is rapidly gaining popularity in paediatric orthopaedic patients. This imaging technique is very valuable in precisely localizing focal areas of mechanical stress, which can be pain generators, at cortical bone level, when plain radiography and MRI have failed to identify the source of symptoms. Paediatric nuclear medicine imaging is an evolving field with new exciting prospects. Conflict of interest statement The authors have no potential conflicts of interest. References 1 Treves ST , Lassmann M. International guidelines for pediatric radiopharmaceutical administered activities . 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TI - Paediatric nuclear medicine imaging
JF - British Medical Bulletin
DO - 10.1093/bmb/ldx025
DA - 2017-09-01
UR - https://www.deepdyve.com/lp/oxford-university-press/paediatric-nuclear-medicine-imaging-WZCjSm8MY6
SP - 127
VL - 123
IS - 1
DP - DeepDyve
ER -