SCINTIGRAFIA OSSEA.

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1 SCINTIGRAFIA OSSEA

2 Sc. Ossea - DEFINIZIONE scintigrafia ossea: tecnica di imaging diagnostico che rileva la distribuzione di un radiofarmaco osteotropo nel sistema scheletrico sia planar (bidimensionale) che tomografica (3D) sc. whole-body ( sinonimi: total-body, pancorporea, corpo intero): produce immagini planar di tutto lo scheletro, incluso quello appendicolare nelle proiezioni anteriore e posteriore. Se necessario si eseguono scansioni planar di sezioni limitate dello scheletro nelle proiezioni più adeguate Sc. Ossea Segmentaria: scansioni di zone limitate dello scheletro SPECT (single photon emission computed tomography) Ossea: produce un’immagine tomografica tridimensionale di una porzione scheletrica Sc. Ossea Polifasica : usualmente si riferisce allo studio trifasica (TPBS: three phases bone scan), consiste di una immagine dinamica di flusso arterioso, statica del pool venoso e tardiva del metabolismo osseo vero e proprio

3 Sc. Ossea - INDICAZIONI neoplasie (primitive o secondarie) dell’osso
fratture occulte osteomielite necrosi avascolare patologia flogistico-degenerativa stato della protesi articolari malattie metaboliche dell’osso sia focali (es. m. di Paget) che diffuse (ad es. iperparatiroidismo) RSD ( reflex sympathetic distrophy) infarto osseo vitalità degli innesti ossei dolore osseo non spiegato dalle altre metodiche valutazione della attività osteoblastica, prima della terapia radiometabolica con 89Sr, 153 Sm-EDTMP, 186 Re HEDP

4 RADIOFARMACI

5 Preparazione del Paziente
informazione al paz. sulle modalità di esecuzione dell’indagine e dei tempi di permanenza non occorre il digiuno, anzi… il paz. deve essere normoidratato svuotare la vescica immediatamente prima della scansione. In caso di impossibilità a svuotare la vescica, potrà essere necessario il cateterismo vescicale. raccolta di informazioni pertinenti al caso: a- risposta a quesiti formulati dal paz. b- anamnesi relativa a fratture,traumi, osteomielite, cellulite, edema , artrite, neoplasie, malattie metaboliche dell’osso c- sintomatologia d- indagini recenti somministrazione di altri radiofarmaci, TC, MRI e- concomitanti terapie che possono interferire con i risultati f-pregressa radioterapia g-anamnesi relativa a precedenti interventi ortopedici e non ortopedici h-risultati degli esami di laboratorio assicurarsi che prima della scansione vengano rimossi oggetti metallici o comunque radiopachi, collane, medagliette (attenzione a quelle attaccate alle magliette!), magneti (per “magnetoterapia”), fibbie delle cinture, ganci di pancere e bustini ecc annotare la presenza di pace-maker

6 ACQUISIZIONE:Collimatore
collimatori per bassa energia (LE) a fori paralleli, ad alta risoluzione (HR) o general purpose (GP). collimatori divergenti praticamente abbandonati collimatori pin-hole per lo studio di piccoli particolari ad alta risoluzione (!efficienza molto bassa!) collimatori convergenti pressoché scomparsi

7 Tempo di scansione dalla 2°ora in poi,
la cinetica del radiofarmaco è tale che i conteggi a livello osseo continuano ad aumentare per parecchie ore dopo la 2° con contemporanea riduzione dell’attività circolante nel sangue il contrasto tra una possibile lesione e l’osso sano circostante è già sufficiente a 2 ore, quindi aumentando l’intervallo di tempo tra iniezione e scansione, l’accuratezza diagnostica dell’esame non migliora, nonostante le immagini dello scheletro siano apparentemente più nitide sconsigliabile anticipare lo scan prima della 2° ora, il ridotto contrasto tra osso e tessuti molli riduce l’accuratezza diagnostica immagini ottenute dopo la 5-6° ora , a causa della marcata riduzione di conteggi (T ½ del Tc99m = 6ore !) comportano un deterioramento della statistica di conteggio e quindi dell’accuratezza diagnostica, a meno di non raddoppiare i tempi di scansione

8 Sc. WHOLE-BODY-WB le immagini del corpo intero sono ricostruite da acquisizioni seriate che comprendono tutto il corpo attraverso movimenti di traslazione del lettino-paziente e la testata della gamma-camera. E’ indifferente che a muoversi sia la gamma-camera od il lettino In mancanza di sistema WB, è possibile raccogliere immagini spot dei vari distretti corporei facendo attenzione a sovrapporre parte dell’immagine nelle due scansioni adiacenti, per evitare di tralasciare piccole aree, anch’esse potenzialmente sedi di patologia i sistemi WB possono funzionare con due modalità differenti (spesso le due opzioni sono presenti nel medesimo strumento): a- immagini spot sequenziali (ovvero la testata raccoglie un immagine, poi il sistema si sposta al distretto adiacente e il programma del computer restituisce alla fine un’immagine completa dello scheletro), b- movimento continuo e progressivo Proiezione anteriore e posteriore distanza collimatore/paziente: la minor distanza dalla superficie corporea è solitamente la medesima nella proiezione posteriore, mentre in anteriore, data la conformazione corporea, una posizione fissa non sempre è la migliore. Attualmente esistono dispositivi (body contour) che variano automaticamente ed istantaneamente la posizione della testata della gamma-camera in modo da mantenere al minimo la distanza collimatore/paziente Conteggi: una buona immagine deve contenere >1.5 milioni di conteggi, con coll. GP. Matrice: 256 x 1024x16, accettabili (specie per i sistemi meno recenti) 128x256x16

9 Sc. Ossea PoliFasica - TPBS
posizionare l’area da studiare nel campo di vista della gamma camera, il più vicino possibile alla superficie corporea impostare un’acquisizione dinamica per la durata di sec, con frame da 2-5 sec., matrice 64 o 128 iniettare a bolo il radiofarmaco iniziare l’acq. immediatamente (fase dinamica di flusso arterioso) subito dopo, entro 5-10 min dalla somministrazione, acquisire un’immagine statica di pool venoso, matrice 128 o meglio 256x256, della durata di 3-5 min in modo da raccogliere 300k conteggi dalla 2° ora in poi acquisire le immagini statiche del metabolismo osseo

10 SPECT raccolta di immagini su un arco di 360°, orbita circolare od ellittica a seconda del distretto corporeo esplorato (body contour ove applicabile); matrice 64 o 128, 60 – 120 campionamenti angolari di sec/step se la scansione interessa l’area toracica è necessario far alzare le braccia dietro la testa in modo da escluderle dal campo di vista una particolare attenzione deve essere riservata alla regione pelvica, dove l’attività in vescica che si modifica durante il tempo della scansione , è causa di inevitabili artefatti di ricostruzione (streak artifacts) ricostruzione di slices tomografiche abituali (Tx,Sag,Cor) e ricostruzione volumetrica 3D gli algoritmi di ricostruzione variano in rapporto allo strumento impiegato, collimatore, sistema e programmi di elaborazione, si applica comunque la correzione per l’attenuazione.. Pin-Hole generalmente si raccolgono k conteggi, che comportano però tempi di acq. abbastanza lunghi (5-15 min)

11 Posizionamento del paziente
generalmente il paziente in posizione supina, particolare cura deve essere usata ad evitare rotazioni del bacino e del torso, causa di artefatti tecnici altre posizioni sono possibili in rapporto a casi particolari Proiezioni e viste particolari possono essere necessarie proiezioni oblique, tangenziali ecc., vengono ricordati casi particolari: vista caudale del bacino (squat view), in pratica il paziente siede sul detettore: discrimina l’attività della vescica da quella della sinfisi pubica /branche ileo ed ischio-pubiche posteriore od oblique posteriori del costato a braccia abdotte per discriminare tra captazioni focali delle prime coste nell’arco posteriore e delle scapole colonna dorso lombare in ortostatismo per discriminare tra lesione focali delle coste ed attività nei calici renali, in ortostatismo il rene tende a dislocarsi caudalmente e quindi se la captazione è di pertinenza renale si sproietta oblique ant o post del torace per meglio evidenziare focolai di ipercaptazione costali vista plantare dei piedi, che consente la minor distanza collimatore/paz frog-leg , per lo studio dell’articolazione coxo-femorale/testa femorale, specie se usano coll. pin-hole

12 Interventi farmacologico e non
impiego di diuretici (furosemide) per favorire l’eliminazione dell’urina radioattiva cateterismo vescicale, solo nei casi strettamente indispensabili la sedazione non influenza il metabolismo del radiofarmaco, può essere impiegata in età pediatrica quando i normali mezzi di contenimento non siano sufficienti; gli antidolorifici in paz. con sintomatologia dolorosa importante (la posizione richiesta dalla scansione ed i lettini semirigidi possono esacerbare i sintomi) Interferenze Farmacologiche E’ sconsigliata la somministrazione di difosfonati a scopo terapeutico .Controindicazione relativa rimessa recentemente in discussione, ipotizzando che l’interferenza sarebbe trascurabile dal punto di vista pratico

13 Biodistribuzione inattese
accumuli del radiofarmaco in regione extraossea non infrequente. Il significato clinico variabile: talora spia di una patologia occulta o semplice deposizione aspecifica di sali di Ca. calcificazioni dei tessuti molli (periarticolari e viscerali), in corrispondenza di ferite chirurgiche recenti depositi di sali di Ca attraverso somministrazione s.c. (Calcieparina s.c. parete addominale) alcuni tumori primitivi o metastatici ricchi di depositi di Ca ( ad es. metastasi epatiche da t. del colon retto, t. mammari) diffuso nella mammella sotto stimolo estrogenico a carico degli arti in corso di linfedema accumulo nei versamenti pleurici e peritoneali, solitamente neoplastici deposito nei vasi venosi in corso di trombosi dei vasi ragioni tecniche: recente somministrazione (di solito entro le 48 ore precedenti) di radiofarmaci tecneziati o di prodotti del catabolismo ancora presenti nell’organismo

14 Cause di errore/artefatto -1
la maggiore sorgente di errori causata dall’urina radioattiva presente nei reni e nelle vie urinarie che può determinare falsi positivi : ristagno di urina nei calici renali o lesione alle ultime coste?  scansione in ortostatismo ristagno lungo il decorso degli ureteri o lesione dei processi traversi ovvero delle del bacino?  rivedere dopo opportuno intervallo di tempo, durante il quale il paz. assume liquidi e deambula

15 Effects of Faulty Radiopharmaceutical Preparation on Bone Scan

16 Soft-Tissue Uptake That Often Is Clinically Significant

17 Cause di errore/artefatto -2
marcato residuo vescicale che oscura la regione della sinfisi pubica  a- vista caudale, b- scansione tardiva a 24 ore, c- cateterismo vescicale solo se strettamente necessario diversione delle vie urinarie con reservoir applicato alla cute dell’addome  a- provvedere alla sostituzione del reservoir, b- proiezioni laterali del bacino contaminazione con urina radioattiva degli indumenti e/o della cute, si possono verificare le seguenti condizioni: la presenza di contaminazione è chiaramente riconoscibile, ma c’è il rischio che possa mascherare eventuali lesioni ossee:  ripetere la scansione dopo a- rimozione degli indumenti contaminati , b- risciacquare la cute con acqua e sapone neutro dubbio diagnostico tra focolaio patologico e contaminazione puntiforme, tipico il caso di hot-spot in corrispondenza della tuberosità ischiatica  ripetere la scansione a-dopo rimozione indumenti e pulizia cutanea b-spostare il pene (glande contaminato)

18 Cause di errore/artefatto -3
il contrasto tra osso e tessuti molli è basso, l’immagine è poco nitida: scansione troppo precoce:  rivedere il paz. a opportuna distanza di tempo presenza nel corpo del paz. di radionuclide ad alta energia (131 I, 67 Ga) che possono deteriorare l’immagine  a- verificare lo spettro energetico, se si conferma la presenza di altri isotopi più energetici si può tentare di stringere la finestra b- ripetere l’indagine (con ulteriore somministrazione) quando il precedente isotopo sarà eliminato /decaduto presenza di impurità radiochimiche  provvedere al controllo di qualità del radiofarmaco presenza di area ipocaptante (fredda) presenza di oggetti radiopachi:  rimozione degli oggetti e ripetizione della scansione secondaria a pregressa radioterapia resezione chirurgica

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21 VISUALIZZAZIONE MIOCARDIO Cuore MDP Mazza C 16.4.02

22 breast ca St IV, ; arimidex, gabapentin,zometa ; VAS9
GiorgiMamm Giorgi Giuliana F(DH OncI)breast ca St IV, ; arimidex, gapbapentin,zometa ; VAS9 breast ca St IV, ; arimidex, gabapentin,zometa ; VAS9

23 Calandrini R, F 75y,Paget tibia

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25 Lesioni ossee multiple da percossa

26 ParaOsteoArtroPatia POAP
POA is characterized by deposition of calcium in soft tissues primarily around the joints. All joints are susceptible to the disease, but most commonly it involves the hip joint, the knees, and the shoulders. Heterotopic bone formation (HBF) is a common complication of spinal cord injury and has been reported in 16% to 54% of paraplegic cases (1). Less commonly it can follow acute anoxia, head injury, CVA, encephalomyelitis, poliomyelitis, multiple sclerosis, and burns (2). The common factor among these conditions is immobilization. No definite cause for HBF has been found. Local factors such as continuous pressure, decubitus ulceration, and trauma from physical therapy, have been suggested; however, the occurrence of POA in areas remote from pressure joints or decubitus ulcers and in the absence of physical manipulation has been documented. Systemic factors such as hypoproteinemia and urinary tract infection have been implicated, but studies failed to prove the relation (2). Finally, it is believed that the ossification result from transformation of primitive mesenchymal derived cells present in soft tissues into bone forming cells in response to a variety of stimuli. POA leads to complete ankylosis of the affected joints limiting their range of motion and the independence of the patient. The clinical manifestations resemble those of inflammation which include pain, warmth, swelling, and limited range of motion. These symptoms and signs simulate thrombophlebitis, cellulitis, or osteomyelitis. Three studies, serum alkaline phosphatase levels, bone scintigrams, and X-ray, are essential for diagnosing POA. Alkaline phosphatase is the earliest to become abnormal. It begins rising within one week of the injury (1). Typically it is attributed to healing fractures, occult biliary disease or normal bone growth in young patients. The three-phase bone scan becomes abnormal with increased blood flow and blood pool as early as 19 days following the injury (12,2), the third-phase turns abnormal one to two weeks later. The radiographs turn positive later in the process at 4-5 weeks following the accident. The importance of bone scanning lies at the two ends of the pathologic process. In the early stages (before any calcifications are seen on X-ray) and, when only the flow study is abnormal, starting therapy with Didronel can effectively prevent further bone formation. Didronel is a diphosphonate compound (Etidronate Disodium) that has a potent in vivo and in vitro inhibitory effect on calcification. In the later stages of the process treatment consists of surgical resection of the heterotopic bone. However, the resection should be performed only when the ectopic bone is mature and when the active bone formation has ceased (4). This can be demonstrated by falling levels of alkaline phosphatase or by quantitative bone scans. Regions of interest are drawn on the affected joint and on a normal bone (usually L5), and ratio of activity of calculated (3). When the process is stable the ratios remain constant over time and resection of the ectopic bone scan can be performed with little possibility of recurrence

27 Necrosi Avascolare - AVN
Avascular necrosis (AVN) affects both children (Legg-Perthes) and adults. In the following discussion only osteonecrosis in adults will be discussed (5). Various etiologies of AVN include trauma (30-50% femoral neck fractures lead to AVN), steroids, alcohol, pancreatitis, hemoglobinopathies (i.e. sickle cell disease, polycythemia, etc.), dysbarism, and Gaucher's disease. Although the disease mechanism is not worked out, some proponents suggest that fat embolism is a common denominator. Fat emboli from fatty liver, destabilization and coalescence of plasma lipoproteins, and/or disruption of fatty bone marrow and other fat deposits are three mechanisms by which AVN can occur. In the case of dysbaric osteonecrosis formation of microthrombi from red cell aggregated and platelets on the gas bubble surface and not the actual bubble is the cause of mechanical vascular occlusion. With steroids abrupt cessation or dose changes can lead to hyperlipidemia and emboli from sudden release of stored fat globules in hepatocytes. Steroids prevent release of fat into the system by the hepatocytes (4). Other possible mechanisms for steroid osteopathy are related to steroid-induced hypophosphatemia (5). The central factor in AVN is vascular insufficiency from occlusion leading to cellular anoxia and death of hematopoietic cells at 6-12 hours, osteocytes and other bone cells at hours, and marrow fat cells at 2-5 days (1). Usually the femoral head cartilage is not affected because it is nourished by synovial fluid. The femoral head consists of a cortical shell of bone surrounding a mass of cancellous bone consisting of myeloid elements, fat, and sinusoids. The femoral head has an end-arterial vascular supply with poor collaterals. Similar vasculature exists in other bones which are also prone to AVN; these include: knees, humeri, tali, scaphoid, and lunate bones. Vascular insufficiency may be due to blocked arterial inflow or blocked venous outflow, leading to a rise in intramedullary pressure and compromising perfusion further (4). Five stages are described in AVN. Stage I, consists of an asymptomatic hip, bone infarction demonstrated histologically, normal to subtle mottled lucency in the femoral head, photopenia on bone scan (due to no bone repair or formation of hydroxyapatite matrix). In Stage II, the hip is asymptomatic to mildly symptomatic and the femoral head contour is preserved, The infarct appears as an area of increased density at the periphery of the femoral head (due to laying down of new bone between necrotic trabeculae), MDP activity is increased (due to hyperemia and formation of hydroxyapatite crystal). In Stage III, the patient is symptomatic, the femoral head is flattened subtly with development of the crescent caused by fracture through dead subchondral bone, histology shows necrotic trabecula and marrow on both sides of the fracture line (fracture occurs because rate of bone resorption exceeds rate of repair) and there is failure of differentiation of mesenchymal cells into osteoblasts, MDP activity remains increased due to continued cellular activity. In Stage IV, pain is greater than in Stage III, collapse of the necrotic segment with step deformity of the femoral head, bone repair is ineffective, MDP activity remains increased due to cellular activity. In Stage V the pain is persistent, cystic changes are seen radiographically in both the femoral head and acetabulum, MDP activity remains increased due to continued ineffective repair (4). Mitchell, et al. observed greater sensitivity for MRI compared to scintigraphy. In a series of 56 patients, MR was abnormal in all patients. In 80% of patients, a high signal inner border was present inside a high intensity peripheral rim (the double line sign). In 41 patients with AVN, the sensitivity of bone scintigraphy was 90%. In advanced stages, MRI failed to detect head flattening in six cases which was demonstrable on plain films. Other investigators have also shown MRI to have greater sensitivity compared to radionuclide imagery. Markisz, et al. found a sensitivity of 100% for MRI compared to 81% for scintigraphy, while specificity for both was 100% (2). Thickman, et al. found a greater sensitivity for MR (98%) than for scintigraphy 86% although scintigraphy was more specific (79% vs. 71%) (6). Overall, MRI is the most sensitive modality for early stages of osteonecrosis, but should be correlated with plain films in advanced stages. Scintigraphy is useful in Stage I disease over plain films, but is superseded by MRI in sensitivity in general. MR may also be useful in following progress with and without therapy for AVN.

28 RabdoMiolisi Rhabdomyolysis results from skeletal muscle injury with release of muscle cell contents into the plasma. These cell contents include enzymes such as creatinine kinase, glutamic oxalacetic transaminase, lactate dehydrogenase, and aldolase; the heme pigment myoglobin; electrolytes such as potassium and phosphates; and purines. It may or may not result in myoglobinuria, depending on the amount of myoglobin released into the plasma, the GFR and the urine concentration. Rhabdomyolysis was first reported in 1881, in the German literature but the major clinical sequelae were described in 1941 by Bywaters (3), during the blitz of London, in patients with crush injuries. Rhabdomyolysis may occur after trauma, ischemia (including acute myocardial ischemia), excessive exertion (marathon runners), bacterial and viral sepsis, electrical burns, other injuries related to heat or cold, prolonged muscle compression as often seen in the unconscious state after alcohol or drug intoxication, seizures, hypokalemia and shock. It has also been reported in associated with metabolic disorders (phosphoglycerate kinase deficiency, and carnitine palmityl transferase deficiency) and exposure to various drugs and toxins (meperidine HCI). Many theories have been advanced to explain soft tissue uptake of bone imaging agents, including binding of the radiopharmaceutical to soft tissue calcium deposits, iron deposits, denatured proteins, enzymes or immature collagen and deposition second to altered tissue perfusion or capillary permeability. Buja, et al (6) performed electron microscopy on experimentally induced canine myocardial infarctions and concluded that Tc-phosphates do absorb onto several kinds of calcium, such as Ca hydroxyapatite, amorphous Ca phosphates, and Ca complexed with myofibrils and other macromolecules. Many tissues when infarcted, among them liver, spleen, gut, brain, muscle and fat, show hyperconcentration of Tc phosphates compounds. Other pathological entities with increased Tc phosphate affinity contain demonstrable calcium, such as nephrocalcinosis, tumoral calcinosis, milk-alkali syndrome, calcified nodules, and infiltrated calcium. Dewanjee and Kahn (5) explain the uptake of Tc chelates in myocardial infarcts by the formation of polynuclear complexes with denatured macromolecules rather than the deposition of calcium in the mitochondria. Zimmer, et al. (7) advanced the hypothesis of binding of Technetium phosphates by enzymes such as alkaline phosphatase. McRae et al (8) demonstrated increased soft tissue and renal deposition with intramuscular administration of iron gluconate in rats. The fact that renal concentration was increased as well may relate to the increased renal concentration also seen in hemosiderosis, thalassemia major, and to the splenic concentration seen in chronic sickle cell anemia, and glucose-6-phosphate dehydrogenase deficiency. Any mechanism involving active in bony deposition, such as adsorption onto immature collagen, hyperemia and altered capillary permeability could play a role in soft tissue deposition of Tc-phosphates. No single mechanism has gained universal acceptance. Quite probably, several are involved and in some cases multiple mechanisms may be in operation simultaneously

29 Impronta Vescicale da Massa Pelvica
A bone scintigram was negative for bone metastases. However, the urinary bladder was noted to show displacement (arrow) suggesting a pelvic mass. A CT scan confirmed a mass which proved to be a poorly differentiated adenocarcinoma of Mullerian origin. Discussion Incidental non-osseous findings on bone scans have been reported by Poulouse, et al. (1). Pulmonary uptake denoting malignant calcifications (2), muscle uptake in various conditions, such as rhabdomyolysis and, uptake in effusions associated with malignancy (3) are but a few such examples. Abnormalities of the urinary system have been noted on 15% of bone scans (4). Of those, 80% are caused by malignant process such as primary tumor or metastases. Thus, the importance of such observations cannot be over-emphasized. In our case, the incidental bone scan finding was the displacement of the urinary bladder by an ovarian tumor. This does not appear to be a chance occurrence. Patients with breast carcinoma have been reported to be more prone than those in the general population to develop carcinoma in other organs, specifically, the ovaries and the GI tract. Some investigators believe that endocrine hormones are implicated in the pathogenesis of breast cancer and it seems reasonable to suggest that other organs such as the ovaries, which are under hormonal influence might, therefore, be at risk for malignant conversion. Although the role of hormones is not very well understood in the etiology of breast cancer, the higher incidence of this tumor in premenopausal women is suggestive of estrogenic role in the process (5). On the other hand, the familial association of breast and ovarian carcinoma has been reported to result from the affect of mothers transmitting a "cancer predisposing gene" to half their daughters (6). Supporting this is the review of Prior and Waterhouse (5) which examined 17,756 registrations for breast and 3,470 for ovarian cancer. An increased risk of a second primary tumor in the ovary was observed in patients diagnosed with a first primary in the breast before 45 years of age (expected (E) = 1.83, observed (O) = 8, P < 0.01). Of interest, no increased risk was found in patients diagnosed after 45 years of age. Analysis of the data also showed that the development of a primary tumor at either site before 45 years of age carried a 2.8 fold increase in risk of a second primary at the other site, (E = 3.21, O = 9, P < 0.01). Additionally, women who successfully recover from breast, uterine or ovarian cancer have about twice the expected risk of developing colorectal cancer (7). For the patients of the largest group, breast carcinoma survivors, the risk adjusted to family history of GI cancer is 3 (P < 0.003) as compared to control group which was 1. Therefore, continued screening of these patients is valuable in early detection of second primary tumors. In summary, extraosseous findings on bone scans represent a malignant etiology in 65% of cases (1). The urinary tract is a major non-skeletal component of the bone scan since 45-50% of the radiopharmaceutical is excreted by the kidneys. In patients with breast cancer, by far one of the largest groups routinely images for bone metastases, an awareness of the propensity for developing a second pelvic abdominal malignancy should alert the nuclear medicine physician to attach special significance to the observation of alterations in normal urinary anatomy and function.

30 OsteoArtroPatia Ipertrofica Polmonare
Clinical: Secondary hypertrophic osteoarthropathy (HO), also known as the Marie-Bamberg Syndrome, consists of clubbing of the finger and toes, periostitis of the long bones, sometimes a polyarthritis resembling rheumatoid arthritis, hyperhydrosis, flushing, and blanching. Ossifying periostitis is seen on x-ray at the distal end of the shaft of the long bones as an opaque line of new bone formation, separated from the underlying cortex by a narrow radiolucent band. As it accumulates, the periosteal new bone becomes irregular, rough and undulating and eventually fusing with the cortex. The radiological differential diagnosis includes thyroid acropachy, chronic venous stasis, hypervitminosis A and infantile cortical hyperostosis. Four to twelve percent of the patients with bronchial carcinoma develop HO. But HO may precede the discovery of the neoplasm by several months. There are over 60 extra and intra-thoracic diseases which have been associated with HO. When there is no know associated disease this condition is referred as pachydermoperiostitis, a rare familial disorder. Pathophysiology: Histologically there is an inflammatory reaction with round cell infiltrates and latter the periosteal new bone formation develops. The pathogenesis of HO remains elusive. Estrogens, circulating factors, neurogenic factors and growth hormone have been postulated to play a role (5). Of special interest is the regression of the new periosteal bone which frequently occurs after removal of a lung carcinoma. The pre-operative pain may also regress completely in 4-5 days (3). Thoracotomy, hilar neurectomy, vagotomy, ipsilateral occlusion of the pulmonary artery, radiotherapy, chemotherapy, intercostal nerve section, laparatomy (1), and chemical vagatomy sometimes lead to remission of the symptom (2), but the mechanism by which these diverse procedures lead to remission is uncertain. Nuclear Medicine: Radionuclide bone imaging is a very sensitive method for detecting abnormalities of HO. A diffuse symmetric increased uptake in the diaphysis and metaphysis of tubular bones along their cortical margin create a distinctive "parallel track". Associated synovitis can lead to increased radionuclide uptake in the periarticular region. Ali (1) reported the following distribution of bony involvement in 48 patients: tibia and fibula 95%, femur 88%, hands and carpels 88%, radius and ulna 85%, feet 81%, scapula 67%, mandible 42%, clavicle 33%, ribs 2% and pelvis 2%. Of note, none of these 48 patients had increased spinal uptake. A patchy uptake in the long bones is not unusual. These scintigraphic findings frequently appear before roentgenographic findings, correspond well with clinical manifestation and decreased after treatment.

31 OSTEOMIELITE 67Ga-CITRATO Findings:
Radiographs of the left tibia demonstrated a markedly sclerotic and deformed bone consistent with cicatrix formation. Bone scintigrams showed diffusely increased uptake of Tc-99m MDP involving the distal tibia, with several areas of locally increased uptake, particularly at the most distal aspect of the tibia. Gallium scintigraphy showed no increased uptake to suggest active osteomyelitis. The erythrocyte sedimentation rate was 6 mm per hour, with a normal white count and differential. A CT scan showed an isolated intramedullary formation of bone consistent with sequestrum formation. Surgery was electively performed for radical debridement of the left tibia. Discussion: This case demonstrates the uncertainty in the evaluation of chronic osteomyelitis by several modalities. The patient did fail to meet clinical criteria of increased sedimentation rate and leukocytosis, but did have increased bone pain. She also failed to meet the criteria used to diagnose osteomyelitis scintigraphically. However, she did meet the criteria for CT diagnosis of sequestrum within bone. The question that arises is how firm the data are for these various modalities of diagnosis. In particular, how firm is the evidence for evaluation of chronic osteomyelitis by combined bone and gallium imaging? The criteria usually accepted for the diagnosis of osteomyelitis by combined scanning states that the gallium scan must show an increased target-to-background ratio over that seen on the bone scintigraphy indicating the presence of infection. A normal gallium scan implies inactive disease. Lisbona and Rosenthal studied forty consecutive patients referred for possible inflammatory disease with both bone and gallium scans. Sixteen patients showed some form of active osteomyelitis, including chronic active osteomyelitis, all of whom demonstrated both positive bone and gallium scans. The authors state, "The Tc-99m-MDP images were in general more intensely positive than the gallium images." Three patients had disease classified as inactive osteomyelitis, all of whom had radiographs similar to the patient described above, and negative gallium images. Hoffer takes mild exception to the last statement, stating, "Chronic osteomyelitis may rarely take up gallium." Alazraki studied patients with chronic osteomyelitis with bone scans, correlating the ratio of the uptake in the abnormal extremity over those in the normal extremity to the clinical course of the patient while on antibiotic therapy. She concluded that this ratio fell as the patient underwent a positive clinical response. Other articles have not focused on chronic osteomyelitis, but on the use of combined imaging in osteomyelitis in general. Rosenthal studied patients with previously inserted orthopedic devices and concluded that congruency in uptake between the two studies was important in interpretation. Congruent uptake between the two studies with no focally increased gallium uptake suggested the absence of osteomyelitis. Non congruency or marked focally increased gallium uptake suggested osteomyelitis, cellulitis, or nonseptic synovitis. Graham induced osteomyelitis in the tibias of rabbits and followed the animals with gallium scans while under treatment. All 25 rabbits with negative gallium scans at the end of six weeks of antibiotics were culture-negative. Eighteen rabbits with positive gallium scans at the end of six weeks were nearly equally divided between positive and negative culture groups. Rosenthal's study does support the contention that increased gallium uptake in the same distribution as increased bone uptake is necessary for the interpretation of osteomyelitis. Graham's data do support the statement that a negative gallium scan implies inactive disease. In the patient above, bone biopsy was performed prior to surgery, and all debrided fragments were submitted for culture. All cultures were negative at the time of discharge ten days following surgery. At least in this instance, our criteria performed quite well. 67Ga-CITRATO

32 Meningioma Findings: Bone scintigrams at initial presentation were reported as normal. Asymmetric hyperostosis (arrow) of the frontal bone was reported on bone schintigraphy at the time of her recurrence and correlative skull radiograph was obtained. Retrospectively, this asymmetry was present on the initial bone scintigram. There was no scintigraphic change in the cranial asymmetry on routine follow-up scintigraphy. At the time that she complained of headache, nausea, and personality change, a mass was seen on CT in the right frontal area (arrow) which enhanced with contrast. The irregular low density around the mass was not typical for a meningioma or metastatic breast cancer. Changes in the bone at the tumor base suggested that it had been present for some time. The patient underwent a craniotomy and biopsy of the lesion which was a meningioma containing a focus of metastatic breast carcinoma. Discussion: Hyperostosis frontalis interna is a benign condition of uncertain etiology in which there is symmetric thickening of the inner table of the frontal bone of the skull (1). Hyperostosis calvariae diffusa and fronto-parietalis are related entities. The radiographic criterion for diagnosis is at least one cm thickness of the respective cranial bones on a 24 x 30 cm roentgenogram. Bone scintigraphy, which reflects the vascularity and increased metabolic state of the lesion, is more sensitive (2). There is a 12% incidence of hyperostosis frontalis interna in the normal population, with approximately 95% of the cases being female. Peak incidence occurs between the ages of 40-60, with development beginning after completion of growth and ossification of the skull. Microscopic specimens show evidence of bone growth in hyperostotic lesions. Thickening of the spongiosa is noted on autopsy (1). There may be a hormonal origin to this non-pathologic process as suggested by the prevalence in post-menopausal women. Correlation with the presence of obesity and headache symptoms has been established in older women. Radiographic asymmetric hyperostosis frontalis interna is considered non-physiologic and is rare. It is, however, listed as a "normal" roentgen variant (5). It may be confused with such entities as Paget's disease, metastases, or a meningioma. The appearance may be sessile or nodular and it may occur in single or multiple patches. In the current case, scintigraphic asymmetric cranial uptake represents a long-standing intracranial meningioma to which her breast malignancy eventually metastasized. The coexistence of tumors of different origins is not rare and 33 cases of inter-tumor metastases have been reported in patients with meningiomas (6). The incidence of meningiomas in breast cancer patients is twice the expected value, suggesting an association between the two malignancies. Both are more common in females and have peak incidence in the fifth and sixth decades. A hormonal inter-relationship is implied by the presence of estrogen receptor proteins in both (7). It is hypothesized that implantation of blood borne metastases into a meningioma occurs due to the presence of a rich vascular supply and high lipid content. In summary, symmetric cranial hyperostosis is a common entity, occurring in 15-20% of normal females between the ages of 40 and 60. Asymmetric cranial hyperostosis on bone scintigraphy is rare and may represent the presence of a meningioma or other intracranial lesion. Head MRI is recommended when no other obvious etiology such as Paget's disease can be elicited. In the presence of breast cancer, removal of the cranial meningioma is indicated as it represents a possible site of metastasis from the primary breast malignancy.

33 INIEZIONE NELL’A. RADIALE DELLA MANO DX  UPTAKE NEI TESS
INIEZIONE NELL’A. RADIALE DELLA MANO DX  UPTAKE NEI TESS. MOLLI DI MANO E POLSO Injection of 99mTc-MDP into radial artery of right hand produces dramatic soft-tissue uptake in arterial distribution along lateral side of hand and wrist (anterior view). SK skull; PEL ABD pelvis and abdomen.

34 DILATAZIONE URETERE SN E CAVITA’ CALICIALI
Grossly dilated left ureter and renal collecting system seen on anterior whole-body 99mTc-MDP bone scan of patient with prostate cancer. Indwelling Foley catheter was in place at time of scanning

35 METASTASI EPATICHE MASSIVE DA CA. COLON
Anterior (right) and posterior (left) abdominal views of 99mTc-MDP bone scan of patient with hepatic metastasis from colon carcinoma show intense uptake of radioactivity in liver, which is heavily involved with tumor.

36 CA. MAMMELLA SN Left anterior oblique (right) and right anterior oblique (left) views of chest from 99mTc-MDP bone scan of patient with left-breast cancer show soft-tissue uptake in both breasts. Uptake in left breast is more extensive (arrow) and corresponds to tumor mass on that side. LAO RAO

37 A. POSTERIORE B. SPECT-TX
(A) Planar posterior image of lower back from 99mTc-MDP bone scan of patient with chronic back pain. Focus of increased uptake is seen in region of left pedicle of 3rd lumbar vertebra (arrow). (B) SPECT image shows this uptake to be more superficial in overlying soft tissue (arrow). Patient had received injections of antiinflammatory drugs at this site a few weeks before scan.

38 STRAVASO DAL SITO DI INIEZIONE  COMPTON SCATTER
Compton scatter from a partially infiltrated dose (anterior view on left, posterior view on right). Because of this scatter from the site of infiltration in the right arm, there is apparent increased uptake in the adjacent right breast (arrow) that might erroneously be interpreted as a pathologic breast finding.

39 COLLIMATORE E RISOLUZIONE : A: LEHR, B: LEGP, C: MEGP
Effect of collimation on the resolution of planar bone scans: low-energy highresolution collimator (A), low-energy generalpurpose collimator (B), and medium-energy collimator (C).

40 EFFETTO DELLA DISTANZA SULLA RISOLUZIONE: A: contatto B: 10 cm C: 20 cm D: 30 cm
Effect of distance from the patient on the resolution of planar bone scans: just touching the back (A), 10 cm behind the back (B), 20 cm behind the back (C), and 30 cm behind the back (D). The anatomic detail of the lumbar spine progressively degrades as the distance between the patient and the collimator increases.

41 EFFETTO DEL FOTOPICCO: A. 140 keV (99mTc) B. 122 keV (57Co)
Effect of using a 57Co photopeak on planar bone scans: a 20% 140-keV photopeak (A) and a 20% 122-keV photopeak (B). Using a 57Co photopeak of 122 keV both increases softtissue scatter in the image and causes a loss of 99mTc photons. Image quality is dramatically reduced.

42 EFFETTO DELLA MATRICE: A. 64x64 B. 256x256
Effect of matrix size on planar bone scans. Posterior views of the lumbar spine obtained using a (A) and a (B) matrix demonstrate a loss of anatomic detail for the former.

43 EFFETTO DEI CONTEGGI: 100K (A), 250k (B), 350k (C), 500k counts (D)
Effect of count density on planar bone scans. Posterior views of the pelvis were acquired for 100,000 counts (A), 250,000 counts (B), 350,000 counts (C), and 500,000 counts (D). With increasing count density, image quality improves.

44 CORREZIONE DELLA UNIFORMITA’: A. CORRETTA B. ERRATA
Posterior views of the lumbar spine obtained with the correct (A) and incorrect (B) uniformity correction matrices. This obese patient was unable to empty the bladder.

45 ARTEFATTO DA MOVIMENTO
Movement of the patient’s head during planar bone scanning.