Author Correction: Serotonin transporter binding is increased in Tourette syndrome with Obsessive Compulsive Disorder.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

GABAA Receptors in the Mongolian Gerbil: a PET Study Using [18F]Flumazenil to Determine Receptor Binding in Young and Old Animals.

PURPOSE: Plastic changes in the central auditory system involving the GABAergic system accompany age-related hearing loss. Such processes can be investigated with positron emission tomography (PET) imaging using [18F]flumazenil ([18F]FMZ). Here, [18F]FMZ PET-based modeling approaches allow a simple and reliable quantification of GABAA receptor binding capacity revealing regional differences and age-related changes. PROCEDURES: Sixty-minute list-mode PET acquisitions were performed in 9 young (range 5-6 months) and 11 old (range 39-42 months) gerbils, starting simultaneously with the injection of [18F]FMZ via femoral vein. Non-displaceable binding potentials (BPnd) with pons as reference region were calculated for auditory cortex (AC), inferior colliculus (IC), medial geniculate body (MGB), somatosensory cortex (SC), and cerebellum (CB) using (i) a two-tissue compartment model (2TCM), (ii) the Logan plot with image-derived blood-input (Logan (BI)), (iii) a simplified reference tissue model (SRTM), and (iv) the Logan reference model (Logan (RT)). Statistical parametric mapping analysis (SPM) comparing young and old gerbils was performed using 3D parametric images for BPnd based on SRTM. Results were verified with in vitro autoradiography from five additional young gerbils. Model assessment included the Akaike information criterion (AIC). Hearing was evaluated using auditory brainstem responses. RESULTS: BPnd differed significantly between models (p < 0.0005), showing the smallest mean difference between 2TCM as reference and SRTM as simplified procedure. SRTM revealed the lowest AIC values. Both volume of distribution (r2 = 0.8793, p = 0.018) and BPnd (r2 = 0.8216, p = 0.034) correlated with in vitro autoradiography data. A significant age-related decrease of receptor binding was observed in auditory (AC, IC, MGB) and other brain regions (SC and CB) (p < 0.0001, unpaired t test) being confirmed by SPM using pons as reference (p < 0.0001, uncorrected). CONCLUSION: Imaging of GABAA receptor binding capacity in gerbils using [18F]FMZ PET revealed SRTM as a simple and robust quantification method of GABAA receptors. Comparison of BPnd in young and old gerbils demonstrated an age-related decrease of GABAA receptor binding.

Serotonin transporter binding is increased in Tourette syndrome with Obsessive Compulsive Disorder.

While the importance of the serotonergic system in obsessive compulsive disorder (OCD) is well established, its role in Tourette syndrome (TS) is uncertain. Particularly in TS patients with comorbid OCD (TS + OCD), decreased serotonin transporter (SERT) binding has been suggested. Here, we investigated for the first time SERT binding in TS patients with and without OCD (TS - OCD) compared to both healthy controls (HC) and OCD patients as well as the influence of escitalopram using the potent SERT imaging ligand [123I]2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ([123I]ADAM) and single-photon emission tomography (SPECT). We included 33 adult subjects (10 HC, 10 TS - OCD, 8 TS + OCD and 5 OCD). In patients with OCD and TS + OCD [123I]ADAM SPECT was repeated after 12-16 weeks treatment with escitalopram. SERT binding was normal in patients with OCD and TS - OCD, but significantly increased (p < 0.05) in those with TS + OCD, particularly in caudate and midbrain compared to both HC and TS - OCD. Treatment with escitalopram resulted in a significant overall reduction in SERT binding (range, 19 to 79%, p values between 0.0409 and <0.0001) without any correlation with clinical improvement. Our results provide further evidence that alterations in the serotonergic system in TS are related to comorbid OCD and do not represent the primary cause of the disease.

Cerebral microglia activation in hepatitis C virus infection correlates to cognitive dysfunction.

Hepatitis C virus (HCV) infection may induce chronic fatigue and cognitive dysfunction. Virus replication was proven within the brain and HCV-positive cells were identified as microglia and astrocytes. We hypothesized that cerebral dysfunction in HCV-afflicted patients is associated with microglia activation. Microglia activation was assessed in vivo in 22 patients with chronic HCV infection compared to six healthy controls using [(11) C]-PK11195 Positron Emission Tomography (PET) combined with magnetic resonance tomography for anatomical localization. Patients were subdivided with regard to their PCR status, Fatigue Impact Scale score (FIS) and attention test sum score (ATS). A total of 12 patients (54.5%) were HCV PCR positive [of which 7 (58.3%) had an abnormal FIS and 7 (58.3%) an abnormal ATS], 10 patients (45.5%) were HCV PCR negative (5 (50%) each with an abnormal FIS or ATS). Patients without attention deficits showed a significantly higher accumulation of [(11) C]-PK11195 in the putamen (P = 0.05), caudate nucleus (P = 0.03) and thalamus (P = 0.04) compared to controls. Patients with and without fatigue did not differ significantly with regard to their specific tracer binding in positron emission tomography. Preserved cognitive function was associated with significantly increased microglia activation with predominance in the basal ganglia. This indicates a probably neuroprotective effect of microglia activation in HCV-infected patients.

Monoaminergic neurotransmission is altered in hepatitis C virus infected patients with chronic fatigue and cognitive impairment.

BACKGROUND: The majority of patients with hepatitis C virus (HCV) infection suffer from disabling fatigue, cognitive dysfunction, and quality of life reduction. Meanwhile, there is increasing evidence that HCV infection can affect brain function. Recent studies have shown that fatigue and psychomotor slowing may resolve in patients with hepatitis C after treatment with ondansetron. This observation indicates alteration of serotonergic neurotransmission in HCV infected patients with chronic fatigue. METHODS: Data from 20 HCV infected patients who were referred to our clinic because of disabling fatigue and cognitive decline of unknown cause were analysed retrospectively. Patients had undergone a diagnostic programme, including clinical and psychometric examination, electroencephalogram (EEG), magnetic resonance imaging of the brain, cerebrospinal fluid analysis, and I-123-beta-CIT (2beta-carbomethoxy-3-beta-(4-[(123)I]iodophenyl)tropane) single photon emission computerised tomography (SPECT) studies of serotonin and dopamine transporter binding capacity. RESULTS: All patients had pathological results on the fatigue impact scale. Two thirds of patients showed pathological attention test results. EEG, magnetic resonance imaging, and cerebrospinal fluid analysis were normal. Pathological dopamine transporter binding was present in 12/20 (60%) patients and pathological serotonin transporter binding in 8/19 (50%) patients. Patients with normal SPECT results did not significantly differ from controls with regard to psychometric test results. Interestingly, patients with both decreased serotonin and dopamine transporter binding showed significantly impaired performance in most of the tests applied. Comorbidity that could have impaired cerebral function was excluded in all patients. CONCLUSION: Our findings indicate alteration of serotonergic and dopaminergic neurotransmission in HCV infected patients with chronic fatigue and cognitive impairment.

Synthesis and preliminary biological evaluation of [123I]Me2Pyr, a new potential ligand for imaging of central cannabinoid CB1 receptors.

A synthesis of 1-(2,4-dichlorophenyl)-5-(4-[123I]iodophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid N',N'-dimethyl-hydrazide ([123I]Me2Pyr), a new radioiodinated analogue of the high-affinity cannabinoid CB1 receptor antagonist SR141716A, is described. Labelling was achieved by radioiododestannylation of the tributylstannyl precursor with [123I]iodide in the presence of chloramine T. HPLC purification afforded the labelled product in 48% radiochemical yield. Preliminary rat brain biodistribution studies with the 125I labelled compound revealed high uptake in the substantia nigra, the globus pallidus externus and the cerebellum, which is consistent with the known distribution of CB1 receptors.

Computerized movement analysis and beta-CIT-SPECT in patients with restless legs syndrome.

Considering the positive effect of dopaminergic treatment on Restless Legs Syndrome (RLS), it has been suggested that the cause of RLS may be linked to central dopaminergic dysfunction. As problems of alternating movements can result from a failure in the dopaminergic system, we used a movement analysis system to analyse this and in-parallel, performed [123I]beta-CIT-SPECT to investigate signs of dopaminergic dysfunction in patients with RLS. In 10 patients with idiopathic RLS, we conducted a three-dimensional computerized ultrasound-based movement analysis before a single dose of levodopa (L-dopa) was given and 90 minutes after the L-dopa challenge. In 6 of the 10 RLS patients, the striatal dopamine transporter system was studied with [123I]beta-CIT-SPECT. We did not observe any significant change in the movement pattern with the computerized movement analysis and no significant effect of L-dopa on the movement. We did not detect any significant differences between patients and normal controls regarding beta-CIT-signals in putamen or caudate nucleus, respectively. There was, however, a slight but significant change regarding the relative [123I]beta-CIT-SPECT binding in the putamen vs. the caudate nucleus. We conclude that the methods used could not detect any definite signs of changed central dopaminergic function in patients with RLS.

[[123I]beta-CIT SPECT imaging of dopamine and serotonin transporters in Parkinson's disease and multiple system atrophy.

AIMS: Definition of the regional pattern of dopamine transporter (DAT) dysfunction in advanced Parkinson's disease (PD) and evaluation of a potential correlation between DAT binding and symptoms; elucidation of the role of DAT imaging in the differential diagnosis of PD and multiple system atrophy (MSA); assessment and comparison of serotonin transporter (SERT) binding in PD and MSA. METHODS: [(123)I]beta-CIT SPECT was performed in 14 patients with advanced PD, 10 with moderate MSA and 20 healthy persons. Specific to nonspecific tracer binding ratios (V(3)") were calculated via ROI analysis of uptake images at 4 h (SERT binding) and 24 h (DAT binding) p. i. RESULTS: In PD bilateral reduction of striatal DAT binding (63-70%) was seen. The caudate ipsilateral to the clinically predominantly affected side showed relatively the least impairment. Significant correlations (r = -0.54 to -0.64) between DAT binding and Hoehn and Yahr stage, UPDRS-scores and duration of disease were found. In MSA DAT binding was less reduced (40-48%) targeting the putamen contralateral to the side of clinical predominance. Significantly lower SERT binding was observed in PD midbrain and MSA hypothalamus compared to controls -- and in MSA relative to PD mesial frontal cortex. CONCLUSIONS: In advanced PD striatal DAT binding is markedly reduced with the least reduction in caudate ipsilateral to the clinically predominantly affected side. In moderate MSA with asymmetrical symptoms DAT dysfunction is predominant in the contralateral putamen, a pattern seen in early PD. The reduction of SERT in the midbrain area of PD patients suggests additional tegmental degeneration while in MSA the serotonergic system seems to be more generally affected.

PET-studies in idiopathic chronic hydrocephalus before and after shunt-treatment: the role of risk factors for cerebrovascular disease (CVD) on cerebral hemodynamics.

AIM: To investigate the impact of cerebrovascular risk factors in idiopathic chronic hydrocephalus concerning cerebral hemodynamics and clinical outcome after shunting. Global cortical cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) in 53 patients (67 +/- 11 yrs) were determined by 15-0-water-PET studies before and after administration of acetazolamide (1 g) prior (pre), one week (7 d) and seven months (7 m) after shunting. According to the prevalence of vascular risk factors (American subcommittee on reporting standards for cerebrovascular disease) patients were classified into a "low-risk" (n = 27) and "high-risk" (n = 20) group; patients with a history of stroke (n = 6) were separated. After 7 months, clinical outcome was assessed according to Stein and Langfitt. While CBF in "high-risk" patients prior to surgery was significantly lower in clinical responder compared to non-responder (32 +/- 5 vs. 42 +/- 15 ml/100 ml/min; p < 0.05), CVR was marginal in both outcome groups (< 30%). One week after shunting, CVR in responder of "high-risk" significantly increased (64 +/- 30 vs. 31 +/- 10% pre; p < 0.01). In "low-risk" patients, differences in CVR prior to shunting were found: CVR was lower in clinical responder than in non-responder (36 +/- 11 vs. 47 +/- 22% pre; p > 0.05) and deteriorated in non-responder (29 +/- 15% vs. 47 +/- 22 pre; p < 0.02) one week after shunting. Different peri-operative characteristics in global CVR regarding clinical response after shunting between both "risk-groups" were observed. Pathophysiological mechanisms upon clinical sequels after shunting in idiopathic hydrocephalus may not be unique.

The role of cerebral blood flow and cerebrovascular reserve capacity in the diagnosis of chronic hydrocephalus--a PET-study on 60 patients.

AIM: To investigate the clinical value of cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) in the management of chronic hydrocephalus. Global cortical CBF and CVR in 60 patients (66 +/- 12 yrs) with chronic hydrocephalus were investigated before, one week (7 d) and 7 months (7 m) after shunting by 15-O-H2O PET (Siemens ECAT 951/31) at rest and after application of acetazolamide (1 g). After 7 months, clinical outcome was assessed according to Stein and Langfitt and patients were classified into responder (n = 31) and non-responder (n = 29). Before Surgery, responder had lower blood flow values compared to non responder (36 +/- 8 vs. 41 +/- 11 ml/100 ml/min; p = 0.04), whereas CVR was not different between outcome groups (33 +/- 10 vs. 41 +/- 8%; p > 0.05). After shunting, CVR in non-responder decreased from 41 +/- 8% to 32 +/- 5% (7 d), whereas in responder significant increases (p < 0.02) to 55 +/- 46% (7 d) and 54 +/- 31% (7 m) were observed. Regarding early individual changes in CVR, the majority (12/18; 66%) of non-responder had marked decreases in CVR-levels (< 30%), whereas clinical responder considerably improved in CVR (> 30%) in half of patients (7/14). Measurement of cerebral blood flow in chronic hydrocephalus might substantially contribute to selection of shunt candidates and neurological sequels may be rather related to early regeneration of the hemodynamic reserve.

Regional cerebral blood flow profiles of shunt-responder in idiopathic chronic hydrocephalus--a 15-O-water PET-study.

AIM: To find out if regional characteristics of cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) may indicate shunt response in idiopathic chronic hydrocephalus. 11 patients with idiopathic chronic hydrocephalus (65 +/- 13 yrs) were followed-up within a year after shunting. Patients were classified into clinical responder (n = 5) and non-responder (n = 6) according to Stein and Langfitt. All patients had measurement of CBF and CVR with dynamic 15-O-water PET (Siemens ECAT 951/31) before and after application of acetazolamide (1 g). Regional differences between outcome groups were analysed with "statistical Parametric Mapping" (SPM99b; Wellcome Department, London, UK). Group differences were regarded as significant, when uncorrected p-value on voxel and on cluster level were p < 0.001 and p < 0.05, respectively. Regarding CBF distribution there was significantly reduced CBF in the frontobasal cortex in responder compared to non-responder (cluster level p = 0.026). In CVR, a variety of cortical regions showed significant decreases compared with non-responder: also in frontobasal cortex (on cluster level p = 0.009). However, most significant reductions were found in temporodorsal and limbic cortical regions (on cluster level p < 0.001). Preoperative hemodynamics displayed a regional profile of reduced CBF and CVR in patients with shunt improvement. Prospective studies for determining the accuracy of regional blood flow characteristics for outcome prediction are warranted.

Neuropsychological sequels to changes in global cerebral blood flow and cerebrovascular reserve capacity after shunt treatment in chronic hydrocephalus--a quantitative PET-study.

AIM: To study relationship of neuropsychological deficits in chronic hydrocephalus before and after shunting with dynamics in cerebral blood flow. In 27 patients (65 +/- 13 yrs) with idiopathic chronic hydrocephalus 11 selected neuropsychological tests, providing a wide range of psychomotor functions, were performed before, one week (early) and 7 months (late) after shunting. Parallel global cortical blood flow (CBF) and cerebrovascular reserve capacity (CVR) were determined by dynamic 15-O-water PET studies (Siemens ECAT 951/31) before and after application of acetazolamide (1 g). Test raw data and changes after treatment were compared with global and regional blood flow values by polynomial regression. No relationship of test profiles with hemodynamics before surgery was found. After one week, improvement of gait was related to an increase in cerebrovascular reserve capacity (p = 0.05). After 7 months changes in mental tests were related to changes in hemodynamics: again increases in CVR were significantly related to improvements in visual attention and verbal memory (p < 0.01). Early improvement of hemodynamic reserve was related to improvement in gait, whereas mental improvement was particularly related to increases in global CVR at later periods after shunting. These results indicate that neurological sequels in idiopathic chronic hydrocephalus after shunting may actually depend on consecutive improvement of cerebral hemodynamics.

Resting regional cerebral glucose metabolism in advanced Parkinson's disease studied in the off and on conditions with [(18)F]FDG-PET.

Studies of resting regional cerebral glucose consumption (rCMRGlc) in nondemented patients with Parkinson's disease (PD) have produced conflicting results, reporting both reduced and normal metabolism in advanced disease and reduced or normal metabolism after dopaminergic therapy. To investigate these issues, [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed in 11 nondemented PD patients with advanced disease and 10 age-matched controls. PD patients were studied after withdrawal of all dopaminergic medication to produce a practically defined off condition, and a second time 1 hour after levodopa, resulting in a clinical on state. Dynamic PET scans and simultaneous arterialised venous blood samples of [(18)F] activity were obtained. A graphical approach was used to generate parametric images of rCMRGlc and statistical parametric mapping to localise significant metabolic changes in PD. Compared with controls, global rCMRGlc was reduced in the on but not in the off condition in PD. In both states, significant regional reductions of glucose uptake were found in the parietal, frontal, temporal cortex, and caudate nucleus. Reductions correlated with the severity of disability in frontal and temporal cortex. Direct comparison between on and off conditions revealed relatively greater reductions of uptake in the ventral/orbital frontal cortex and the thalamus during on. Results suggest that cortical and caudate hypometabolism are common in advanced PD and that caution is mandatory if [(18)F]FDG PET is being used to differentiate advanced PD from dementia and progressive supranuclear palsy where similar reductions are seen. Furthermore, in PD, administration of levodopa is associated with further hypometabolism in orbitofrontal cortex; an area known to be relevant for reversal learning where performance is typically impaired after dopaminergic treatment.

Assessment of the incorporation of revascularized fibula grafts used for mandibular reconstruction with F-18-PET.

AIM: Determination of the range of regional blood flow and fluoride influx during normal incorporation of revascularized fibula grafts used for mandibular reconstruction. Evaluation, if healing complications are preceded by typical deviations of these parameters from the normal range. Assessment of the potential influence of using "scaled population-derived" instead of "individually measured" input functions in quantitative analysis. METHODS: Dynamic F-18-PET images and arterialized venous blood samples were obtained in 11 patients early and late after surgery. Based on kinetic modeling regional blood flow (K1) and fluoride influx (Kmlf) were determined. RESULTS: In uncomplicated cases, early postoperative graft K1--but not Kmlf--exceeded that of vertebrae as reference region. Kmlf values obtained in graft necrosis (n = 2) were below the ranges of values observed in uncomplicated healing (0.0113-0.0745 ml/min/ml) as well as that of the reference region (0.0154-0.0748). Kmlf values in mobile non-union were in the lower range--and those in rigid non-union in the upper range of values obtained in stable union (0.0211-0.0694). If scaled population-derived instead of measured input functions were used for quantification, mean deviations of 23 +/- 17% in K1 and 12 +/- 16% in Kmlf were observed. CONCLUSIONS: Normal healing of predominantly cortical bone transplants is characterized by relatively low osteoblastic activity together with increased perfusion. It may be anticipated that transplant necrosis can be identified by showing markedly reduced F- influx. In case that measured input functions are not available, quantification with scaled population-derived input functions is appropriate if expected differences in quantitative parameters exceed 70%.

Dopamine transporter binding in Gilles de la Tourette syndrome.

Preliminary studies in patients with Gilles de la Tourette syndrome (TS) provided evidence of presynaptic dopaminergic dysfunction, demonstrating increased reuptake sites. Therefore we investigated striatal dopamine transporter binding in 12 TS patients and 9 control subjects using single photon emission computed tomography and 123I-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane. In TS patients we found significantly higher relative striatal activity ratios (mean +/- SD 12.33 +/- 3.58) than in controls (9.36 +/- 1.35, P< 0.05). Only five patients, however, showed striatum/occipital cortex ratios more than 2 SD above the normal means. Seven patients had activity ratios within the average ratio of the control group plus 2 SD. Regarding the relationship between clinical parameters and striatum/occipital cortex ratios, we found an association between binding ratios and "self-injurious behavior" and "lack of impulse control." This study corroborates previous data suggesting an involvement of the dopaminergic system in TS pathology. Our results demonstrate that an increase in dopamine transporter capacity is a possible but not a necessary alteration, and which appears more likely when self-injurious behavior and lack of impulse control are associated.

Dopamine D2 receptor imaging in Gilles de la Tourette syndrome.

OBJECTIVES: To examine postsynaptic dopamine D2 receptors in Tourette syndrome (TS). MATERIAL AND METHODS: Seventeen patients and a control group were investigated using single photon emission computed tomography (SPECT) and iodobenzamide (123I-IBZM). RESULTS: In neuroleptic treated patients (n = 7) 123I-IBZM-binding was significantly reduced compared to both normal controls (P < 0.0001) and unmedicated patients (P < 0.001). In unmedicated patients (n = 10) mean binding ratio did not differ from that of control group. Patients in advanced stages of the disease, however, revealed significantly reduced relative striatal binding compared to patients in the early stages (P<0.005) and normal controls (P<0.0001). CONCLUSION: The results lend further support to the hypothesis that the dopamine receptor is involved in TS pathology. During the natural course of the disease tics often improve in early adulthood. It is suggested that this spontaneous recovery from tics may be associated with reduced receptor binding capacity.

Altered striatal dopamine D2 receptor density and dopamine transport in a patient with hepatic encephalopathy.

A patient suffering from liver cirrhosis presented with a bradykinetic-rigid syndrome suspected as Parkinson's disease. A detailed work-up of the case revealed hepatic encephalopathy as the cause of the neurological symptomatology. An alteration of striatal dopamine D2 receptor binding and dopamine re-uptake sites was demonstrated by 123I-iodobenzamide (IBZM) and 123I-beta-CIT single photon emission computed tomography (SPECT), respectively. It is suggested that the alteration of the dopamine re-uptake in cirrhotics may be the cause of an increased catabolism of dopamine in HE.

A positron emission tomography study of cerebrovascular reserve before and after shunt surgery in patients with idiopathic chronic hydrocephalus.

OBJECT: In this study the authors use positron emission tomography (PET) to investigate cerebral blood flow (CBF) and cerebrovascular reserve (CVR) in chronic hydrocephalus. METHODS: Ten patients whose mean age was 67 +/- 10 years (mean +/- standard deviation [SD]) were compared with 10 healthy volunteers who were 25 +/- 3 years of age. Global CBF and CVR were determined using (15)O-H2O and PET prior to shunt placement and 7 days and 7 months thereafter. The CVR was measured using 1 g acetazolamide. Neurological status was assessed based on a score assigned according to the methods of Stein and Langfitt. Seven months after shunt placement, five patients showed clinical improvement (Group A) and five did not (Group B). The average global CBF before shunt deployment was significantly reduced in comparison with the control group (40 +/- 8 compared with 61 +/- 7 ml/100 ml/minute; mean +/- SD, p < 0.01). In Group A the CBF values were significantly lower than in Group B (36 +/- 7 compared with 44 +/- 8 ml/100 ml/minute; p < 0.05). The CVR before surgery, however, was not significantly different between groups (Group A = 43 +/- 21%, Group B = 37 +/- 29%). After shunt placement, there was an increase in the CVR in Group A to 52 +/- 37% after 7 days and to 68 +/- 47% after 7 months (p < 0.05), whereas in Group B the CVR decreased to 14 +/- 18% (p < 0.05) after 7 days and returned to the preoperative level (39 +/- 6%) 7 months after shunt placement. CONCLUSIONS: The preliminary results indicate that a reduced baseline CBF before surgery does not indicate a poor prognosis. Baseline CBF before shunt placement and preoperative CVR are not predictive of clinical outcome. A decrease in the CVR early after shunt placement, however, is related to poor late clinical outcome, whereas early improvement in the CVR after shunt placement indicates a good prognosis.

Monitoring of graft perfusion and osteoblast activity in revascularised fibula segments using [18F]-positron emission tomography.

The aim of the present study was to evaluate healing of revascularised fibula grafts used for mandibular reconstruction using [18F]fluoride ion and positron emission tomography (PET). Sixteen PET studies in 11 fibula grafts were analysed to determine both blood flow and fluoride influx as a measure of vascularisation and osteogenic activity. Two graft failures and three non-unions were encountered and were compared to the successfully healed grafts. In uneventful graft healing, early PET studies (on average 19 days after grafting) showed a significantly increased blood flow to the grafted bone and to the union between the grafts and the mandibles when compared to the reference region of the cervical spine. In contrast, fluoride influx was significantly lower in the grafts when compared to the plating area and the cervical spine. Six months after grafting, blood flow to the grafted bone and the mandibular bone had returned to a level comparable with the reference region. Fluoride influx remained significantly lower in the grafts than in the plating areas or cervical spines. Graft failures were associated with negligible fluoride influx near zero in early PET studies. These results suggest that revascularised fibula grafts provide a low osteogenic potential, presumably due to the pre-existing lack of cancellous bone. The relatively high frequency of non-unions makes meticulous adaptation of the graft and the mandible mandatory, particularly in patients with compromised viability of the recipient bone.

[Prosthetic scintigraphic study of healing of implants combined with bone transplantation in extreme atrophy and after tumor resection]. / Prospektive szintigraphische Untersuchung zur Frage der Einheilung von Implantaten in Kombination mit Knochentransplantaten bei extremer Atrophie und nach Tumorresektion.

The aim of the present study was to evaluate the healing of onlay grafts to edentulous jaws and after tumor ablation in conjunction with osseointegrated implants using sequential bone scintigraphy and single photon emission computed tomography (SPECT). A total of 24 patients were examined after onlay grafting of extremely atrophic edentulous jaws and after tumor ablation with secondary implant placement 21.4 weeks after grafting. Technetium-99m (MDP) scintigrams were performed immediately after grafting, before and after implant placement, and before abutment connection. Tracer accumulation was assessed semiquantitatively by calculating ratios of count densities between the uptake over the calvaria and over the grafted jaws. There was a significant decrease in tracer uptake during graft healing, which was followed by a significant increase after implant placement and a subsequent decrease during implant healing. In patients with complicated healing, tracer uptake in areas of subsequent graft infection immediately after grafting was significantly lower compared with patients with uneventful healing. These areas also showed a lower increase in tracer accumulation after implant placement due to inferior graft quality, followed by a significant increase of tracer uptake at the time of abutment connection, representing inflammatory peri-implant bone reaction. Sequential bone scintigrams and bone SPECT have the prognostic potential to detect areas of inferior graft revascularization leading to graft infection or failure in the osseointegration of implants. Only bone SPECT allows an exact localization of areas with complicated healing.