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.

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.

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.

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.

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.

PET and CBF studies of chronic hydrocephalus: a contribution to surgical indication and prognosis.

The authors investigate whether measurement of cerebral blood flow (CBF) in chronic hydrocephalus is a reliable indicator in selecting patients to undergo ventriculoperitoneal shunting. Global and regional CBF is quantified (Kety-Schmidt one-compartment model) by positron emission tomography in 21 patients. CBF is determined following injection of 15O-H2O at three time points: 1 week before, 7 days after, and 7 months after shunting. The neurological status of these patients is classified, and cerebrospinal fluid (CSF) dynamics continuous intracranial pressure [ICP] monitoring and CSF infusion tests) were assessed prior to surgery. Preoperative global CBF values correlate well with clinical outcome. Patients with a significantly lower global CBF value show clinical improvement after 7 months, whereas patients with higher CBF values do not (mean, 33 vs. 45 ml/100 ml per minute; p < 0.05). In contrast to conventional methods, including long-term ICP measurement and CSF infusion tests, preoperative global CBF values are discriminating in terms of clinical outcome. Thus, measurement of CBF may be helpful in evaluating the ultimate utility of shunt therapy in chronic hydrocephalus.

[Results of radioiodine therapy of manifest hyperthyroidism and autonomous struma with euthyroidism]. / Ergebnisse der Radiojodtherapie der manifesten hyperthyreose und der autonomen Struma mit Euthyreose.

In 200 patients follow-up examinations were performed up to one year after radioiodine therapy (RITh) with individual dose calculation. The mean applied dose was significantly lower in patients with immunogenic hyperthyroidism (Graves' disease) as compared to patients with non-immunogenic hyperthyroidism (disseminated/multifocal autonomy, HYDA). In Graves' disease the rate of recurrent hyperthyroidism was significantly higher and that of posttreatment hypothyroidism lower. Considering the high recurrence rate in Graves' disease a higher dose, e.g. 150 Gy, seems to be appropriate. In patients with HYDA who received antithyroid drugs during RITh, recurrence of hyperthyroidism appeared slightly more, and posttreatment hypothyroidism slightly less, frequent. The efficiency of RITh was not significantly reduced by additional treatment with antithyroid drugs. Posttreatment hypothyroidism in patients with euthyroid goiter and disseminated/multifocal autonomy (EUDA) occurred significantly more frequent if the basal TSH level was greater than or equal to 0.5 muIE/ml before therapy. The goiter size was reduced independent of the basal TSH level. In this group protection by thyroxine could avoid posttreatment hypothyroidism without impairing the reduction of goiter. In HYDA patients after thyroid surgery recurrence appeared less, and in those with EUDA posttreatment hypothyroidism significantly more, frequent. A lower dose seems to be suitable in patients who underwent thyroid surgery before. In patients with focal autonomy after RITh no recurrence of hyperthyroidism was observed. In 9% a suppressed basal TSHh level indicating persistent autonomy was seen. Posttreatment hypothyroidism in focal autonomy appeared only in patients without manifest hyperthyroidism before RITh and was significantly more frequent in this group as compared to the other groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Thyroglobulin, 131I-whole body scintigraphy and risk factors in the follow-up of differentiated thyroid cancer]. / Thyreoglobulin, 131J-Ganzkörperszintigraphie und Risikofaktoren in der Nachsorge des differenzierten Schilddrüsenkarzinomas.

Results of 131I whole body scans and measurements of thyroglobulin (Tg) in the follow-up of 85 patients with differentiated thyroid cancer were analysed in a retrospective study. All patients were assumed to be tumor-free after therapy. During follow-up, cancer recurrence was observed in 11 patients. Out of 24 131I scans performed for suspected recurrence, cancer was localized in 5. Out of 71 routinely performed 131I scans and Tg measurements during hormone withdrawal, new pathologies were observed in each of two cases one year after the last therapy. 10 out of 11 tumor recurrences were observed in a high-risk group of 40 patients with follicular histology or stage III or IV (UICC 1987). One recurrence occurred in a low-risk group of 41 patients with papillary histology and UICC stage I or II. Later than one year after therapy no recurrence was observed in any patient who belonged to the low-risk group. These results indicate that 131I scans and Tg measurements under endogenous TSH stimulation are necessary in cases of suspected recurrences and probably on a routine basis one year after the last therapy in all patients. In the event of an inconspicuous further course this diagnostic procedure should be restricted to special high-risk groups. Using a cut-off level of 5 ng/ml as compared to 10 ng/ml, the number of false-negative Tg results under suppressive therapy decreased clearly whereas that of the "false-positive" results increased less pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)

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%.

123I-IBZM SPECT: reconstruction methodology and results in parkinsonism and dystonia.

In 58 patients with Parkinsonism or dystonia striatal dopamine D2 receptors were investigated using 123I-iodobenzamide (123I-IBZM) single-photon emission computed tomography (SPECT). The influence of SPECT reconstruction methodology on semiquantification and the clinical value of 123I-IBZM SPECT were evaluated. Delineation of the striatal uptake and striatum/frontal cortex (ST/FC) ratios were improved by the use of compensation procedures for scatter and attenuation as well as the choice of an adequate filter. Satisfactory results were achieved using a Metz prefilter with a comparatively high order number (i.e. high cut-off and low suppression of higher frequencies via roll-off). Regarding clinical diagnoses it was not possible to differentiate between advanced idiopathic Parkinson's disease (IP) and Parkinsonism of other aetiology (OP) on the basis of 123I-IBZM SPECT. But patients with IP and favourable response to L-Dopa showed significantly higher ST/FC ratios than those with fluctuating response. In patients with dystonia ST/FC ratios were significantly higher compared to patients with IP or OP.

[[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.

[18F]fluoride PET indicates reduced bone formation in severe glucocorticoid-induced osteoporosis.

A 61-year-old female patient presenting with mixed connective tissue disease (Sharp syndrome), underwent a long-term high dose glucocorticoid treatment because of multiple organ manifestations. Under steroid therapy she developed severe osteoporosis resulting in multiple fractures. A dynamic [18F]fluoride PET study in this patient revealed reduced fluoride influx in non-fractured vertebrae. This finding corresponds to pathogenetic concepts which propose an inhibition of bone formation as major cause of glucocorticoid-induced osteoporosis. In the light of the presented case it seems to be promising to evaluate the diagnostic benefit of [18F]fluoride PET in osteoporosis.

[Bone SPECT of the jaws after fracture, onlay osteoplasty of insertion of implants]. / Knochen-SPECT des Kiefers nach Fraktur, Auflagerungsosteoplastik oder Implantatinsertion.

AIM: The aim of this study was early differentiation between uncomplicated and complicated processes of healing in the jaw using bone SPECT. METHODS: Investigations were performed in 40 mandibular fractures and 26 jaws after onlay osteoplasty as well as secondary insertion of implants. Bone SPECT was carried out within 1-2 months and after approximately 4-5 months. The uptake in the jaw was assessed semi-quantitatively using ROI analysis. RESULTS: Fractures with uncomplicated healing showed a decrease of uptake in follow-up, whereas fractures with an infection in the later course showed an increase, resulting in a significantly higher uptake at the follow-up investigation for the latter group. 1-2 months after onlay osteoplasty significantly lower uptake was found in regions with later occurrence of sequestration. In regions with implants in which osseointegration failed, there was significant reduction of uptake initially and significant elevation at the follow-up investigation. CONCLUSION: These results indicate a prognostic relevance of bone SPECT in the evaluation of processes of healing in the jaw.

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.

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.