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.

The data presented comes from clinical experience and some milestone papers on the subject.

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.

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.

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.

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.

Although infection may be suggested by signs and symptoms such as fever, pain, general malaise, and abnormal laboratory results, imaging tests often are used to confirm its presence. Morphologic imaging tests identify structural alterations of tissues or organs that result from a combination of microbial invasion and the inflammatory response of the host. Functional imaging studies use minute quantities of radioactive material, which are taken up directly by cells, tissues, and organs, or are attached to substances that subsequently migrate to the region of interest. Bone scintigraphy is extremely sensitive and can be positive within 2 days after the onset of symptoms. With an accuracy of more than 90%, 3-phase bone scintigraphy is the radionuclide procedure of choice for diagnosing osteomyelitis in unviolated bone. In patients with acute renal failure, gallium imaging facilitates the differentiation of acute interstitial nephritis from acute tubular necrosis. Gallium imaging also is useful in the evaluation of pulmonary infections and inflammation. Many opportunistic infections affect the lungs, and a normal gallium scan of the chest excludes infection with a high degree of certainty, especially when the chest x-ray is negative. In the human immunodeficiency virus positive patient, lymph node uptake usually is associated with mycobacterial disease or lymphoma. Focal pulmonary parenchymal uptake suggests bacterial pneumonia. Diffuse pulmonary uptake suggests an opportunistic pneumonia. Gallium imaging provides useful information about other acute respiratory conditions, including radiation pneumonitis and hypersensitivity pneumonitis. In vitro labeled leukocyte imaging with indium-111 and technetium-99m labeled leukocytes is useful in various acute care situations. The test facilitates the differentiation of normal postoperative changes from infection and is useful for diagnosing prosthetic vascular graft infection. In inflammatory bowel disease, labeled leukocyte imaging is useful for initial screening, monitoring treatment response, detecting recurrent disease, and evaluating patients with discordant physical presentation and laboratory test results. Labeled leukocyte imaging, combined with bone marrow scintigraphy accurately diagnoses complicating osteomyelitis. Fluorine-18-fluorodeoxyglucose, imaging is rapidly completed and provides high-resolution images. This test is especially valuable in patients with fever of unknown origin, patients in septic shock, and mechanically ventilated patients suspected of harboring infection. Fluorine-18-fluorodeoxyglucose imaging also shows promise in inflammatory bowel disease.

Fecal lactoferrin (FL) is a noninvasive biomarker that is elevated in Crohn disease (CD) compared to irritable bowel syndrome. The purpose of this study was to evaluate FL in identifying children with active versus inactive CD.

Fresh stool samples were collected from children with CD scheduled for endoscopy or a clinic visit, and from new outpatients who were scheduled for colonoscopy. FL was determined using a polyclonal antibody-based enzyme-linked immunosorbent assay. Physical global assessment, endoscopic findings, erythrocyte sedimentation rate (ESR), and the Pediatric CD Activity Index (PCDAI) were recorded for patients with CD. The PCDAI scores symptoms, laboratory parameters, physical examination, and extraintestinal manifestations. A score of ≤10 is inactive disease, 11 to 30 is mild active, and ≤31 is moderate to severe active.

Of 101 study patients (4- to 20-year-old, 66 boys), 31 had active CD, 23 had inactive CD, and 37 had noninflammatory bowel disease (non-IBD) conditions. Four patients with ulcerative colitis and 6 patients with polyposis were excluded from analysis. FL was significantly elevated in CD versus non-IBD (P < 0.001) and in active versus inactive CD (P < 0.001). The PCDAI and ESR were higher in active CD than in inactive CD (both P < 0.001). Using an FL cutoff of 7.25 μg/g, FL has 100% sensitivity and 100% negative predictive value in detecting active CD. Using an FL cutoff level of 60 μg/g, FL had 84% sensitivity, 74% specificity, 81% positive predictive value, and 77% negative predictive value for detecting active CD.

FL is a promising biomarker of active CD and may be more practical to use when it is not feasible to obtain all of the necessary clinical information for the PCDAI.

An accurate monitoring of mucosal inflammation is important for an effective management of patients with inflammatory bowel disease. Intestinal inflammation can be detected by faecal calprotectin level determination.

To comparatively evaluate the accuracy of faecal calprotectin, clinical scores, common serum markers and endoscopy in the assessment of the severity of intestinal mucosa inflammation in children with inflammatory bowel disease.

Fifty-eight paediatric patients (mean age 13.9 years, 95% CI 2.9-14.8; male 28) with confirmed inflammatory bowel disease (26 Crohn's disease, 32 ulcerative colitis) were enrolled. Before endoscopy, all patients underwent a complete evaluation including: clinical scores, erythrocyte sedimentation rate, C-reactive protein and faecal calprotectin determination. The severity of mucosal inflammation was assessed using specific endoscopic and histologic scores.

Faecal calprotectin showed a high correlation (r=0.655) with the histologic grade of mucosal inflammation, similar to that observed for endoscopy (r=0.699), and it resulted the most accurate tool (sensitivity 94%, specificity 64%, positive predictive value 81%, negative predictive value 87%) to detect the presence of active mucosal inflammation when compared to clinical scores and common serum markers. In patients with apparent clinical and laboratory remission the accuracy of faecal calprotectin resulted further improved (sensitivity 100%, specificity 80%, positive predictive value 67%, negative predictive value 100%).

A more accurate assessment of the severity of mucosal inflammation can be achieved by the determination of faecal calprotectin levels compared to other common clinical and laboratory indices. This non-invasive and objective method could be particular useful in patients with apparent clinical and laboratory remission.

Different nuclear medicine modalities are currently used to study inflammatory and infective disorders of the abdomen. They are usually complementary to radiology and endoscopy, but they play a pivotal role in particular clinical situations. Several radiopharmaceuticals (e.g., 111In or 99mTc labelled white blood cells, monoclonal antibodies, human polyclonal immunoglobulins, 75Ga citrate) are commercially available, but they can not be used indifferently to study abdominal inflammatory disorders. The lack of comparative studies showing the accuracy of each radiopharmaceutical for the study of inflammatory/infective abdominal diseases does not allow the best nuclear medicine technique(s) to be chosen in an evidence-based manner. To this end we performed a meta-analysis of peer reviewed articles published between 1984 and 2004 describing the use of nuclear medicine imaging for the study of inflammatory bowel disorders, appendicitis and vascular graft infections. A guideline for the optimal radiopharmaceutical(s) to be used in each clinical condition and for different aims is provided.

Endoscopic and radiologic studies are frequently required in inflammatory bowel disease (IBD) to determine disease activity, extent of disease, and delineating disease type. Positron emission tomography (PET) using fluorine-18-fluoro-deoxyglucose to identify metabolically active tissues may offer a simple noninvasive alternative to conventional studies in identification and localization of active intestinal inflammation in children with IBD. The aim of this study was to assess the value of PET in identifying active intestinal inflammation compared with conventional endoscopic and radiologic studies, including small bowel follow-through and colonoscopy.

Sixty-five children were enrolled in the study. This included 55 children (mean age, 13.3 yr; range, 7-18 yr; 20 girls) with newly diagnosed IBD (37) or symptoms suggestive of recurrent disease (18) and 10 children with recurrent abdominal pain (mean age, 12.7 yr; range, 8-15 yr; 7 girls) who were studied with PET, and the results were compared with small bowel follow-through with pneumocolon and/or colonoscopy. Thirty-eight patients had Crohn's disease (17 ileal, 12 ileocolic, 5 pancolonic, 3 left-sided disease, 1 right-sided disease), and 17 had ulcerative colitis (15 pan-colitis, 2 left-sided colitis). Mean time interval between PET and other studies was 30 +/- 17.6 days.

PET correctly identified active inflammatory disease in 80% of children with IBD (81.5% with Crohn's disease; 76.4% with ulcerative colitis) and correctly showed no evidence of inflammation in children with recurrent abdominal pain. Gluorine-18-fluoro-deoxyglucose accumulated at sites that corresponded with active disease at colonoscopy in 83.8% of patients and with small bowel follow-through with pneumocolon 75.0% of the time.

This study suggests that PET offers a noninvasive tool for identifying and localizing active intestinal inflammation in children with IBD. PET may not be able to replace conventional studies; however, it may be useful when conventional studies cannot be performed or fail to be completed.

To evaluate (99m)Tc-HMPAO leukocyte scintigraphy as an investigation for inflammatory bowel disease (IBD).

Scintigraphy was performed in 95 children undergoing investigation for IBD in a tertiary Gastroenterology Department. Diagnosis was based on conventional investigations including small bowel barium contrast radiology (BCR), upper gastrointestinal endoscopy (UGIE), colonoscopy, and endoscopic biopsy (the "gold standards"). IBD was confirmed in 73 (57 Crohn's disease; 10 ulcerative colitis; 6 indeterminate colitis) and excluded in 22 (controls). Scintigraphy was (1) evaluated as a screening test, (2) compared with individual conventional tests, (3) assessed for each gut segment.

Screening test: sensitivity 0.75 (95% CI, 0.63-0.85), specificity 0.82 (95% CI, 0.59-0.94), PPV 0.93, NPV 0.5. Comparison with BCR: sensitivity 0.87 (95% CI, 0.72-0.96), specificity 0.57 (95% CI, 0.39-0.73), PPV 0.69, NPV 0.2. Comparison with UGIE: specificity 0.9 (95% CI, 0.79-0.96), NPV 0.13 (sensitivity and PPV unavailable). Comparison with colonoscopy: sensitivity 0.57 (95% CI, 0.41-0.73), specificity 0.71 (95% CI, 0.54-0.85), PPV 0.71, NPV 0.42. Comparison with biopsies paralleled that with endoscopy. False negatives were especially common (NPV< or =0.2) in the proximal gut.

(99m)Tc-HMPAO leukocyte scintigraphy should not be relied on as a screening test for IBD because false negative results are common. This method is especially unreliable at detecting disease in the proximal gut.

The purpose of this study was to evaluate retrospectively the value of leukocyte-labeled scintigraphy, ultrasonography, and contrast radiography compared with endoscopy in children suspected of having inflammatory bowel disease (IBD).

Twenty-eight children (17 boys; mean age, 10.2 years) with IBD based on standard colonoscopic, histologic, and radiologic criteria (16 with Crohn's disease, 5 with ulcerative colitis, 5 with nonspecific colitis, I with granulomatous disease, and I with Beh,cet's disease) were included. Endoscopic, ultrasonographic, and contrast radiologic examinations were realized for 28, 23, and 19 children respectively.

Sensitivity and specificity were 75% and 92% for leukocyte-labeled scintigraphy, 39% and 90% for ultrasonography, and 58% and 83% for contrast radiography. The authors noted discontinuous uptake for 14 of 15 true-positive results for patients with Crohn's disease and continuous uptake for 4 of 4 true-positive results for patients with ulcerative colitis. A negative correlation between scan activity index and Lloyd-Still clinical score was found for 11 patients with Crohn's disease (r = -0.77).

Leukocyte-labeled scintigraphy, a noninvasive and reproducible technique, is a useful tool in the diagnosis and therapeutic strategy of IBD, and provides information on the presence, the intensity, and the extent of the disease, particularly in the terminal ileum. Leukocyte-labeled scintigraphy may not replace colonoscopy with biopsies for diagnosis confirmation. Its reliability seems higher than that of ultrasonography.

The diagnosis of inflammatory bowel disease (IBD) needs a complex diagnostic work-up. Beside verifying the disease itself, it is fundamental to assess disease extent and activity and to detect associated complications, to find the most effective treatment and for follow up. Scintigraphy with radiolabelled leukocytes is able to provide a complete survey of the whole intestinal tract, both the small and large bowel, and detects septic complications successfully with negligible risk. Radionuclide procedures are useful in establishing or ruling out IBD in patients with intestinal complaints, in assessing disease severity, and in the evaluation of extraintestinal septic complications. Widely available radionuclide procedures are discussed, i.e. scintigraphy by 111Indium oxime or 99mTechnetium HMPAO labelled white blood cells and immunoscintigraphy with 99mTc anti-granulocyte antibodies. Advantages and disadvantages of all three methods are stressed out.

The immunoscintigraphies with 99mTc anti-granulocyte antibodies (ANTI-GRANULOCYTE(R) BW 250/183) of 27 patients with suspicion of IBD were retrospectively analysed. Planar anterior and posterior images were obtained 4 and 24 h postinjection, respectively. The bowel was divided into six segments and the activity was visually graded with reference to bone marrow in each segments. The scans were compared with the results of radiological and endoscopical investigations. The diagnosis of IBD was proved or ruled out by means of enteroclysis, large bowel enema or endoscopy.

In the 27 patients, 74 bowel segments with increased activity were detected. In the case of 30 segments in 16 patients, bowel inflammation was revealed by the other methods (true positives). In the case of 44 bowel segments, no underlying bowel inflammation could be verified, and these activities were regarded as aspecific activity. We could not differentiate between true positive and aspecific activity based on scan pattern or intensity.

These findings of aspecific bowel activity using imuunoscintigraphy are in contrast with the results of former studies, while the existence of non-specific activity decreases the reliability of the method. Based on the literature and our experiences, we conclude that 99mTc HMPAO labelling should be the method of choice for the investigation of IBD patients.

Studies have suggested that Tc-99m white blood cell (WBC) imaging is superior to contrast radiology for assessing the extent and activity of inflammatory bowel disease (IBD). The Tc-99m WBC scan seems ideally suited to obtain, in only one examination, a precise temporal snapshot of the distribution and intensity of inflammation, whereas radiographic methods of investigation tend to represent changes that are more chronic. The test is useful in children with inconspicuous signs suggesting IBD in whom laboratory test results are either normal or slightly abnormal. In those cases, a negative Tc-99m WBC study will obviate endoscopic investigations. The author's current experience, in more than 500 patients, indicates that the Tc-99m WBC scan is a virtual gold standard to establish, or exclude, the diagnosis of IBD. The minimal invasiveness of the Tc-99m WBC scan makes it an especially attractive method for evaluating children with IBD. It is economical compared with endoscopy, and its diagnostic sensitivity is excellent. The ability to evaluate the small and large bowel simultaneously is an important advantage for the patient. In conclusion, the Tc-99m WBC scan is a useful tool to evaluate IBD and should be added to the clinician's investigative armamentarium.

To determine the utility of the technetium-labeled autologous white cell scintigraphy (Tc-WCS) for detecting intestinal inflammation in children with suspected inflammatory bowel disease (IBD). Tc-WCS was compared with colonoscopy and histologic examination.

Forty-eight children (26 boys; median age, 10 years; range, 2-17 years) with symptoms and signs suggesting IBD had colonoscopy with exploration of terminal ileum and mucosal biopsies. The scans were judged to be abnormal if activity was seen in the gut within the first hour.

Twenty-one patients had a diagnosis of IBD (Crohn's disease, 13; ulcerative colitis, 5; indeterminate colitis, 3); results of scintigraphy were positive in 16 and negative in 5 (sensitivity, 76.2%); the latter had a moderate degree of intestinal inflammation. In 27 patients, IBD was ruled out. Results of scintigraphy were negative in children with non-specific colitis and in those with lymphoid hyperplasia of the terminal ileum, whereas results were positive in 6 of 12 patients with spondyloarthropathy. In children with IBD, there was a significant correlation between results of scintigraphy and endoscopy for the intensity of inflammation (r = 0.70); however, there was a poor correlation regarding the number of involved segments (r = 0.30) because in 16 patients, endoscopy revealed additional diseased segments as compared with scintigraphy.

A positive Tc-WCS result indicates the presence of an inflammatory process of the gut, whereas a negative test result does not rule out intestinal inflammation, especially when the latter is of moderate degree. Colonoscopy and biopsy are the investigations of choice to establish the diagnosis of IBD and are superior to Tc-WCS in assessing topographic extension of IBD.

Technetium-99m white blood cell ((99m)Tc-WBC) imaging has been part of the initial evaluation and follow-up of more than 400 children presenting with inflammatory bowel disease (IBD) at Children's Hospital of Pittsburgh. Studies have suggested that (99m)Tc-WBC imaging is superior to contrast radiology in assessing the extent and activity of IBD. With only one examination, (99m)Tc-WBC imaging is ideally suited to obtain a precise temporal snapshot of the distribution and intensity of inflammation, whereas radiography tends to detect more chronic changes. There is a high correlation between (99m)Tc-WBC imaging findings and those of endoscopy. When total colonoscopy cannot be completed satisfactorily or when contrast radiography findings are negative or equivocal, scintigraphy can confirm the presence of ileitis or right-sided colitis. Occasionally, (99m)Tc-WBC imaging is useful in differentiating Crohn's disease from ulcerative colitis. Some studies have suggested that (99m)Tc-WBC imaging is useful as an initial screening modality to exclude IBD. Technetium-99m WBC imaging is noninvasive, practical, safe, requires no bowel preparation, and entails less radiation exposure than contrast radiology or computed tomography.