of Bone Pain in Children

Transcription

1 Nuclear Medicine and Molecular Imaging Pictorial Essay Nuclear Medicine and Molecular Imaging Pictorial Essay Laura. rubach 1 Susan. onnolly 1 Edwin L. Palmer III 2 rubach L, onnolly S, Palmer EL III Keywords: 18 F-NaF, bone scintigraphy, pediatric imaging, PET, sports medicine, stress fractures, trauma OI: /JR Received February 7, 2011; accepted after revision pril 18, epartment of Radiology, hildren s Hospital, oston, 300 Longwood ve, oston, M ddress correspondence to L.. rubach (laura.drubach@childrens.harvard.edu). 2 epartment of Radiology, Massachusetts General Hospital, oston, M. JR 2011; 197: X/11/ merican Roentgen Ray Society Skeletal Scintigraphy With 18 F-NaF PET for the Evaluation of one Pain in hildren OJETIVE. lthough not commonly used in current clinical practice, the PET agent 18 F-NaF provides an excellent alternative to the standard tracers used for radionuclide bone scintigraphy. This article illustrates the use and appearance of 18 F-NaF PET and shows examples of its utility in the assessment of bone pain in children. ONLUSION. Skeletal imaging with 18 F-NaF harnesses both the superior imaging characteristics of PET and the improved biodistribution of the fluoride tracer in comparison with standard nuclear techniques, resulting in excellent-quality images that can effectively be used to investigate the cause of bone pain in children. T he rapid development of PET in recent years has led to renewed interest in the use of the positron agent 18 F-NaF as an alternative to 99m Tc-labeled diphosphonate single-photon imaging for radionuclide bone scintigraphy. Fluorine-18-labeled NaF is a positron-emitting, bone-seeking imaging agent that was first introduced in 1962 [1]. lthough early experience with 18 F-NaF showed it to be an excellent bone-seeking radiopharmaceutical, the difficulties of imaging its high-energy 511-keV positron annihilation photons on equipment available at that time resulted in relatively poor image quality. With the introduction of the nger gamma camera and 99m Tc-labeled diphosphonate tracers, much better image quality could at that time be achieved with the use of 99m Tc-labeled singlephoton agents such as methylene diphosphonate (MP). For the past 4 decades, nearly all nuclear bone imaging has been performed with a technetium-99m compound such as MP. Recent advances in the technology of positron imaging cameras, however, coupled with the widespread availability of PET and PET/T devices used for 18 F-FG tumor imaging, have caused renewed interest in and reexamination of 18 F-NaF as a bone imaging agent. Fluorine-18-labeled NaF has a biodistribution generally similar to that of 99m Tc-MP, but its lower protein binding in blood allows a more rapid single-passage extraction by bone, thus permitting earlier image acquisition [2, 3]. Good-quality bone imaging with 18 F-NaF can be performed within minutes after administration of the tracer, as opposed to the 2 3 hours required by MP (Fig. 1). The greater blood extraction of NaF also results in a higher concentration of tracer in bone, roughly 2 times greater than 99 Tc-labeled disphosphonate complexes such as MP [4]. The combination of lower residual soft-tissue tracer activity and greater bone extraction of 18 F-NaF produces images with a higher target-to-background ratio and thus better image contrast than can be achieved with MP imaging. Like the commonly used 99m Tc boneseeking compounds, 18 F-NaF clears rapidly from the blood and is excreted from the body via the kidneys [5]. lthough the radiation absorbed dose per megabecquerel is higher with 18 F-NaF than with the technetium compounds [4], a smaller administered dosage of 18 F-NaF can be effectively used, resulting in an actual radiation absorbed dose for the PET agent that is equivalent to that received from standard single-photon imaging [6]. The physical characteristics of PET also provide significant advantages for 18 F-NaF imaging in comparison with 99m Tc-labeled singlephoton techniques. The intrinsic spatial resolution of current PET is approximately 4 5 mm as measured by full width at half-maximum, which is far superior to the mm at collimator surface available with either planar or tomographic gamma camera imaging using technetium-99m. PET is intrinsically tomographic, allows good-quality attenuation correction across the field of imaging, and JR:197, September

2 has more uniform spatial resolution than single-photon imaging. The widespread availability of T performed as part of PET/T may provide more accurate lesion localization than is possible with conventional planar bone scanning. ecause the uptake of 18 F-NaF reflects bone flow and bone remodeling, both the general image appearance and the approach to image interpretation are similar to those used with 99m Tc-labeled diphosphonate imaging [4]. The greater image contrast of 18 F-NaF often results in greater conspicuity of both physiologic and pathologic uptake than can be seen with diphosphonate imaging, so slight adjustments may be required in the threshold for diagnosing an abnormality. The normal distribution of 18 F-NaF in children varies with age in the same manner as seen with MP. In the past decade, the clinical utility of 18 F-NaF PET bone scanning has been shown by numerous studies. Investigators have reported a higher diagnostic accuracy with 18 F- NaF bone scans than with 99m Tc-MP bone scans in the assessment of both benign and malignant disorders, although many comparisons have been with planar single-photon acquisitions [7 10]. Most experience with 18 F-NaF has been with imaging bone malignancies; however, multiple authors have found 18 F-NaF PET useful for the evaluation of benign bony abnormalities [11 14]. In an experimental model performed in rats, investigators found that stress fractures produced an increase in the uptake of 18 F-NaF and that the uptake was proportional to the level of the initial bony damage [14]. The increased uptake was seen as early as 1 day after a loading injury, with peak uptake at approximately 1 week after injury. These results provide a rational basis for the use of 18 F-NaF PET when imaging trauma patients and those with sports injuries. In the specific setting of trauma related to child abuse, 18 F-NaF PET has been shown to be useful in the detection of skeletal fractures and, in particular, to be highly sensitive for the detection of rib fractures that may be difficult to identify radiographically [13]. The Society of Nuclear Medicine recently published practice guidelines for the performance and interpretation of 18 F-NaF PET [4]. These guidelines conclude that 18 F-NaF may be used to identify skeletal metastases and that the technique may be appropriate for a number of benign disease indications in selected patients. In the pediatric population, evaluations of back pain and of suspected stress injuries in other locations are common indications for skeletal scintigraphy. We believe that these are clinical settings in which 18 F-NaF PET can be effectively used (Figs. 2 12). We present a pictorial survey of the most relevant diseases and injuries encountered in the evaluation of these cases. Imaging The 18 F-NaF PET images shown in this article were obtained on an dvance Nxi PET scanner (GE Healthcare). Whole-body scans or limited images of the region of interest were acquired in either the 2 or 3 mode, beginning minutes after tracer injection, with the use of both emission and transmission scans for attenuation correction. The dosage of 18 F-NaF used was 60 μi/kg (2.2 Mq/kg), with a minimum dose of 300 μi (11.1 Mq) and a maximum dose of 4 mi (148 Mq). ecause these studies were performed as PET and not PET/T acquisitions, fusion software was used to register PET with diagnostic T images, when relevant. When PET/T is available, concomitant acquisition of PET and T provides convenient localization of findings. Summary In conclusion, we believe that the excellent image quality obtained with 18 F-NaF PET skeletal imaging makes it an attractive option for the evaluation of suspected bone trauma and stress-related injuries. References 1. lau M, Nagler W, ender M. Fluorine-18: a new isotope for bone scanning. J Nucl Med 1962; 3: Park-Holohan SJ, lake GM, Fogelman I. Quantitative studies of bone using (18)F-fluoride and (99m)Tc-methylene diphosphonate: evaluation of renal and whole-blood kinetics. Nucl Med ommun 2001; 22: lau M, Ganatra R, ender M. 18 F-fluoride for bone imaging. Semin Nucl Med 1972; 2: Segall G, elbeke, Stabin MG, et al. SNM. SNM practice guideline for sodium 18 F-fluoride PET/T bone scans 1.0. J Nucl Med 2010; 51: zernin J, Satyamurthy N, Schiepers. Molecular mechanisms of bone 18 F-NaF deposition. J Nucl Med 2010; 51: Grant F, Fahey FH, Packard, avis RT, lavi, Treves ST. Skeletal PET with 18 F-fluoride: applying new technology to an old tracer. J Nucl Med 2008; 49: hargava P, Hanif M, Nash. Whole-body F-18 sodium fluoride PET-T in a patient with renal cell carcinoma. lin Nucl Med 2008; 33: Hetzel M, rslandemir, Konig HH, et al. F-18 NaF PET for detection of bone metastases in lung cancer: accuracy, cost-effectiveness, and impact on patient management. J one Miner Res 2003; 18: Schirrmeister H, uck, Guhlmann, Reske SN. natomical distribution and sclerotic activity of bone metastases from thyroid cancer assessed with F-18 sodium fluoride positron emission tomography. Thyroid 2001; 11: Gamie S, El-Maghraby T. The role of PET/T in evaluation of facet and disc abnormalities in patients with low back pain using (18)F-fluoride. Nucl Med Rev ent East Eur 2008; 11: Schirrmeister H, Rentschler M, Kotzerke J, iederichs G, Reske SN. Imaging of the normal skeletal system with 18 F Na-PET compared with conventional skeletal scintigraphy using Tc99m-MP (in German). Rofo 1998; 168: Lim R, Fahey FH, rubach L, onnolly LP, Treves ST. Early experience with fluorine-18 sodium fluoride bone PET in young patients with back pain. J Pediatr Orthop 2007; 27: rubach L, Johnston PR, Newton W, Perez- Rossello JM, Grant F, Kleinman PK. Skeletal trauma in child abuse: detection with 18 F-NaF PET. Radiology 2010; 255: Silva MJ, Uthgenannt, Rutlin JR, Wohl GR, Lewis JS, Welch MJ. In vivo skeletal imaging of 18 F-fluoride with positron emission tomography reveals damage- and time-dependent responses to fatigue loading in the rat ulna. one 2006; 39: JR:197, September 2011

3 Fig year-old female gymnast who presented with low back pain that worsened on extension., Maximum-intensity-projection PET image of spine shows increased uptake in right L5 vertebra (arrow); this finding suggests localization of injury is within pars interarticularis., Transverse PET image at level of L5 confirms localization of abnormal uptake in pars interarticularis (arrow). (Fig. 2 continues on next page) Fig. 1 istribution of 18 F-NaF on PET at different ages., Maximum-intensity-projection (MIP) 18 F-NaF PET image of 4-year-old boy being evaluated for injuries as a result of trauma shows typical body distribution of tracer, paralleling appearance of 99m Tc-labeled methylene diphosphonate imaging. Focally increased uptake in thoracic spine (arrow) indicates compression fracture., MIP PET image of torso of 14-yearold boy being evaluated for low back pain shows normal distribution of radiopharmaceutical. JR:197, September

4 Fig. 2 (continued) 16-year-old female gymnast who presented with low back pain that worsened on extension., Transverse T image at same level as shows horizontal linear defect at L5 pars interarticularis (arrow)., Fused PET/T image shows that increased uptake on PET corresponds to T spondylolysis (arrow). Fig year-old male football player who presented with left-sided low back pain., oronal PET image of lumbar spine obtained at presentation of symptom shows increased uptake in region of left L5 pars interarticularis (arrow), consistent with spondylolysis. Spinal brace was prescribed and symptom slowly improved., oronal PET image obtained 6 months after before resuming participation in sports to evaluate for healing of stress fracture shows less uptake in left L5 stress fracture (arrow) than does initial PET image (), which is consistent with some interval healing of spondylolysis. Fig year-old girl with Ehlers-anlos syndrome and scoliosis who presented with low back pain., Maximum-intensity-projection PET image of lumbosacral spine shows increased uptake at right aspect of L5 S1 (arrow)., oronal (left), sagittal (middle), and transverse (right) PET images suggest localization of uptake at L5 S1 facet articulation (arrows)., oronal (left), sagittal (middle), and transverse (right) T images of lower lumbar and sacral spine show hypertrophic degenerative changes at right facet of L5 S1 (white arrows) and pars defect at level of L5 on right (black arrows)., oronal (left), sagittal (middle), and transverse (right) PET/T fusion images show that increased PET uptake (arrows) corresponds to hypertrophic degenerative changes of L5 S1 facet and not to pars interarticularis of L JR:197, September 2011

5 Fig year-old female softball player who presented with complaint of left low back pain that wakes her up at night., Maximum-intensity-projection PET image of low back and pelvis shows increased uptake at left of L5 vertebra (arrow)., Transverse PET image obtained at level of L5 shows that increased uptake corresponds to vertebral lamina (arrow)., Transverse T image obtained at same level as shows radiolucent lesion with calcified nidus (arrow) at junction of left lamina and pedicle of S1 suggestive of osteoid osteoma., Transverse PET/T fusion image shows that uptake seen on PET () corresponds to osteoid osteoma (arrow) shown on T (). Fig year-old girl with low back pain on extension that developed after fall., Radiograph of lumbar spine shows compression fracture of L5 vertebra (arrow). ecause patient s symptoms and physical examination were thought to be more suggestive of spondylolysis than compression fracture, PET was performed to evaluate for spondylolysis., Maximum-intensity-projection coronal (left) and sagittal (right) PET images of lumbar spine show increased uptake in L5 vertebral body (arrows) consistent with compression fracture. No uptake to support clinical suspicion of spondylolysis is present. JR:197, September

6 Fig. 7 Evaluation of patients who presented with hip or low back pain., 16-year-old girl who presented with left hip pain. Maximum-intensity-projection (MIP) PET image of pelvis shows increased uptake in inferior ramus of pubis (arrow) consistent with stress fracture. Patient was treated conservatively for presumed stress fracture, with resolution of symptoms., 12-year-old otherwise healthy boy who presented with left hip pain. MIP PET image of pelvis shows increased uptake at triradiate cartilage of left acetabulum (arrow) corresponding to location of pain. Patient was treated conservatively for presumed stress fracture, with resolution of symptoms., 12-year-old otherwise healthy boy who presented with low back pain. MIP PET image of pelvis shows horizontal line of increased uptake in sacrum (arrow) consistent with stress fracture. Patient was treated conservatively for presumed stress fracture, with resolution of symptoms., 18-year-old otherwise healthy woman who presented with low back pain. MIP PET image of pelvis shows increased uptake in left sacrum (arrow) consistent with stress fracture. Patient was treated conservatively for presumed stress fracture, with resolution of symptoms. Fig year-old man with osteogenesis imperfecta and scoliosis and history of spinal fusion who presented with left-sided chest wall pain., Maximum-intensity-projection PET image of chest shows intense rounded focally increased uptake in left rib (arrow) that represents rib fracture., Oblique radiograph of left ribs obtained after PET shows very subtle irregularity (arrow) along cortical margin of anterior third left rib at site of abnormality seen on PET; this finding would have been very difficult to detect with radiography alone because there is very little amount of callus formation, which is likely secondary to underlying osteoporosis as a result of osteogenesis imperfecta. No other abnormalities are seen on radiograph to explain intense uptake on PET. Fig year-old female athlete who presented with low back pain., Sagittal maximum-intensityprojection PET image shows increased uptake in spinous process of L3 (arrow) consistent with avulsion injury., Sagittal T image of spine shows lucency with hyperostosis in posteroinferior aspect of L3 spinous process (arrow) at site of PET abnormality. Findings on T are also consistent with diagnosis of fracture., Fused PET/T image shows that area of increased uptake (arrow) corresponds to lucency on T (). 718 JR:197, September 2011

7 Fig year-old man who presented with low back pain after falling on his back., Radiograph of spine does not show any abnormalities., Maximum-intensity-projection PET image of low back shows increased uptake in left transverse process of L3 (arrow) consistent with fracture. Fig year-old boy who presented with low back pain after falling., oronal (left) and sagittal (right) maximum-intensity-projection PET images of spine show increased uptake in superior endplate of L4 vertebra (arrow) consistent with endplate compression fracture., Sagittal MR image of lumbar spine shows increased T2 fatsaturated signal within superior endplate of L4 vertebral body (arrow) at site of increased uptake on PET () consistent with endplate compression fracture. Fig year-old boy with scoliosis who presented with low back pain., oronal (left) and sagittal (right) PET maximum-intensityprojection images of lumbar spine show increased uptake at inferior endplate of L2 (arrows)., Sagittal T image of lumbar spine shows limbus vertebra with defect at anterior inferior endplate of L2 (arrow) corresponding to increased uptake on PET (). JR:197, September