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Unlabelled: INTRODUCTION (PURPOSE OF THE STUDY): The objective of this study was to assess whether dual-time-point (18)F-fluoro-2-deoxyglucose ((18)F-FDG)-PET/CT imaging improved the evaluation of suspected malignancy and if there was any resulting change in management. Methods: A total of 53 patients with suspected malignancy were investigated by performing two static acquisitions started at mean times t = 64 and t = 155 min after the tracer injection. The total number of malignant lesions was 133 and the total number of benign lesions was 61. Visual and semiquantitative analysis was performed on both the early and delayed images. Results: Overall, there was a significant improvement (P < 0.001) in the sensitivity of delayed imaging (94%) compared with early imaging (77%) in detecting malignant lesions, without a reduction in specificity. In 10 patients, 13 malignant lesions were undetected on early imaging alone but detected on delayed imaging. In seven patients, 10 malignant lesions were incorrectly classified as 'likely benign' on early imaging but correctly reported as 'likely malignant' on delayed imaging. Management was altered in 2 out of 17 patients. Overall, delayed imaging altered management in 2 out of 53 studied patients. Dual-time-point (18)FDG-PET/CT imaging was useful in differentiating malignant from benign intra-abdominal lesions but did not improve the evaluation of pulmonary lesions. Conclusions: (18)F-FDG-PET/CT imaging should be performed as late as reasonably possible after tracer administration in order to increase tumour-to-background contrast and thereby improve the sensitivity of demonstrating additional sites of disease. Dual-time-point (18)FDG-PET/CT may be of benefit in the evaluation of intra-abdominal lesions but does not improve the overall evaluation of pulmonary lesions. [ABSTRACT FROM AUTHOR]

Background: Cross-modality image estimation can be performed using generative adversarial networks (GANs). To date, SPECT image estimation from another medical imaging modality using this technique has not been considered. We evaluate the estimation of SPECT from MRI and PET, and additionally assess the necessity for cross-modality image registration for GAN training., Methods: We estimated interictal SPECT from PET and MRI as a single-channel input, and as a multi-channel input to the GAN. We collected data from 48 individuals with epilepsy and converted them to 3D isotropic images for consistence across the modalities. Training and testing data were prepared in native and template spaces. The Pix2pix framework within the GAN network was adopted. We evaluated the addition of the structural similarity index metric to the loss function in the GAN implementation. Root-mean-square error, structural similarity index, and peak signal-to-noise ratio were used to assess how well SPECT images were able to be synthesised., Results: High quality SPECT images could be synthesised in each case. On average, the use of native space images resulted in a 5.4% percentage improvement in SSIM than the use of images registered to template space. The addition of structural similarity index metric to the GAN loss function did not result in improved synthetic SPECT images. Using PET in either the single channel or dual channel implementation led to the best results, however MRI could produce SPECT images close in quality., Conclusion: Synthesis of SPECT from MRI or PET can potentially reduce the number of scans needed for epilepsy patient evaluation and reduce patient exposure to radiation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fard, Reutens, Ramsay, Goodman, Ghosh and Vegh.)

Background: The postulated benefits of the ketogenic diet in the management of multiple medical conditions have seen more patients who are in therapeutic ketosis attending 18 F-FDG PET scans. This study aimed to investigate the effect of ketosis on cerebral glucose metabolism in a clinical PET scanning environment using 18 F-FDG uptake as a surrogate marker., Methods: A retrospective audit was conducted of the brain 18 F-FDG uptake in 52 patients who underwent PET scans for possible cardiac sarcoidosis or suspected intracardiac infection, following a ketogenic diet and prolonged fasting. SUVbw for whole brain and separate brain regions was compared with serum glucose and serum ketone body (beta-hydroxybutyrate) levels., Results: The expected negative association between serum glucose levels and whole brain 18 F-FDG uptake was confirmed. A reduction in SUVbw due to increasing serum ketones levels was also observed that was independent of and in addition to the effects of glucose. The magnitude of the reduction in SUVbw related to serum glucose level and serum ketone level was found to be greater in the precuneus than in the cerebellum or whole brain., Conclusion: In a real-world clinical PET setting, cerebral 18 F-FDG uptake appears to be affected by glycaemia and ketonaemia. This means when assessing the brain, both serum glucose and ketone levels need to be considered when SUVs are used to distinguish between pathologic and physiologic states. The magnitude of this effect appears to vary between different brain regions. This regional difference should be taken into consideration when selecting the appropriate brain region for SUV normalisation, particularly when undertaking database comparison in the assessment of dementia., (© 2022. The Author(s).)

Introduction: [ 18 F]PSMA-1007 has potential advantages over [ 68  Ga]Ga-PSMA-11, although limited prospective data evaluating diagnostic performance exist. The aims of this study are to describe the concordance of [ 18 FPSMA-1007 and [ 68  Ga]Ga-PSMA-11 for TNM with the American Joint Committee on Cancer (AJCC) prognostic stage and assess differences in tracer uptake., Methods: Fifty men (mean age 71.8) were imaged with [ 68  Ga]Ga-PSMA-11 and [ 18 F]PSMA-1007 < 4 weeks apart. Images were independently reported according to TNM by two experienced nuclear medicine specialists blinded to the other scan and prior imaging. Discordant results were resolved by a third independent nuclear medicine specialist. Quantitative analysis of lesion uptake and physiologic tissue for each tracer was performed by one experienced reader., Results: Scan indications were initial staging (n = 12), biochemical recurrence (n = 27) and metastatic disease evaluation (n = 11). Most patients had ISUP grade group 3 or higher. Median PSA value was 2.7 ng/ml (IQR 0.7-12.0), and a minority of patients (28%) were currently treated with androgen deprivation therapy. [ 18 F]PSMA-1007 uptake was significantly higher than [ 68 Ga]Ga-PSMA-11 in local recurrence, nodal and distant metastases and most physiologic sites (including bone) except for urinary bladder which was significantly lower. [ 18 F]PSMA-1007 upstaged local prostate staging in 5/17 patients, local recurrence in 3/33 patients, regional nodal disease in 3/50 patients and 1 distant metastasis (bladder). [ 68 Ga]Ga-PSMA-11 upstaged regional nodal disease in 1/50 patients and distant metastasis in one patient (right adrenal). Overall AJCC prognostic stage was concordant in 46/50 (92%) patients, with two patients upstaged for both [ 18 F]PSMA-1007 and [ 68 Ga]Ga-PSMA-11. [ 18 F]PSMA-1007 had more equivocal results (one regional node; six equivocal bone lesions, one of which was subsequently confirmed metastatic) than [ 68 Ga]Ga-PSMA-11 (one equivocal local recurrence)., Conclusion: Overall AJCC prognostic stage was similar (92%) between [ 18 F]PSMA-1007 and [ 68 Ga]Ga-PSMA-11. [ 18 F]PSMA-1007 demonstrates higher uptake within involved nodes and distant metastases and most physiologic sites except urinary bladder which aided [ 18 F]PSMA-1007 local staging of the prostate primary/local recurrence and regional nodal disease adjacent ureters. However, [ 18 F]PSMA-1007 liver uptake obscured a solitary right adrenal metastasis, and more equivocal bone lesions were identified. Trial registration The study was registered with Australia New Zealand Clinical Trials Registry (ACTRN12618000665235) on 24 April 2018., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Accurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [ 68 Ga]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [ 18 F]PSMA-1007 offers theoretical imaging advantages, but there is limited evidence of clinical and biochemical predictors of scan findings in the staging population. This study investigates the association of clinical variables with imaging characteristics among patients who underwent [ 18 F]PSMA-1007 PET/CT for primary staging of men with histopathologically confirmed prostate carcinoma. A retrospective review of 194 consecutive patients imaged between May 2019 to May 2020 was performed. Association between imaging variables (presence and distribution of metastatic disease, primary tumour SUVmax) and clinical variables (EAU risk criteria) were assessed using descriptive statistics, logistic regression model and ROC analysis., Results: The median age, PSA level and ISUP grade were 70 years, 10 ng/mL and ISUP grade 3, respectively. There were 36.6% of patients with intermediate-risk and 60.8% of patients with high-risk disease. ISUP grade was associated with the presence of metastasis overall (p = 0.008) as well as regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. PSA level was associated with metastatic disease overall (p = 0.001), regional (p = 0.001) and non-regional nodal metastases (p = 0.004), but not with bone metastases (p = 0.087). There were too few visceral metastases for meaningful analysis. SUVmax of the primary prostatic tumour was associated with ISUP grade (p = 0.004), PSA level (p < 0.001) and AJCC stage (p = 0.034). PSA > 20 ng/mL and ISUP grade > 3 had a specificity of 85% (95% CI 78-91%) and 60% (95% CI 50-68%) and a sensitivity of 36% (95% CI 25-49%) and 62% (95% CI 49-74%), respectively, for detection of metastatic disease., Conclusion: Metastatic disease according to [ 18 F]PSMA-1007 PET/CT was associated with ISUP grade and PSA level. This is the largest study using [ 18 F]PSMA-1007 PET/CT to confirm a positive correlation of PSA level, ISUP grade and stage with primary prostate tumour SUVmax., (© 2021. The Author(s).)

Background: Bone scans differentiate transthyretin (ATTR) cardiac amyloidosis from light chain amyloidosis and other causes of increased left ventricular (LV) wall thickness. We examined the prevalence and implications of cardiac uptake in the general population., Methods: Patients were included based on having undertaken a bone scan for non-cardiac indications using Technetium 99m hydroxymethylene diphosphonate (HMDP) or Technetium 99m methylene diphosphonate (MDP). Blinded image review was undertaken. Positive was defined as cardiac uptake ≥ rib AND heart/whole body ratio (H/WB) > 0.0388. Echocardiography and clinical records were reviewed., Results: 6918 patients were included. 15/3472 HMDP scans were positive (14 males, 1 female): none in individuals aged < 65; 1.44% in males and 0.17% in females ≥ 65; 6.15% in males and 1.69% in females ≥ 85. Only 1/3446 MDP scans were positive. All HMDP positive patients had increased septal wall thickness on echocardiography. H/WB correlated positively with LV mass, and negatively with LV ejection fraction. No individual had an explanation other than ATTR for their positive scan., Conclusion: In this Australian subpopulation, the prevalence of positive bone scans consistent with cardiac ATTR is 0% in individuals aged < 65. Prevalence increased with age, reaching 6.15% in men ≥ 85. The amount of HMDP uptake correlated with echocardiographic features of more advanced cardiac involvement. MDP does not appear useful in ATTR., (© 2020. American Society of Nuclear Cardiology.)

Purpose: [ 18 F]PSMA-1007 offers advantages of low urinary tracer excretion and theoretical improved spatial resolution for imaging prostate cancer. However, non-specific bone lesions (NSBLs), defined as mild to moderate focal bone uptake without a typical morphological correlate on CT, are a common finding on [ 18 F]PSMA-1007 PET/CT. The purpose of this study was to investigate the clinical outcomes of patients with [ 18 F]PSMA-1007 avid NSBLs, to determine whether patients with NSBLs represent a higher risk clinical cohort, and to determine whether SUVmax can be used as a classifier of bone metastasis., Methods: A retrospective audit of 214 men with prostate cancer was performed to investigate the clinical outcomes of [ 18 F]PSMA-1007 avid NSBLs according to defined criteria. We also compared the serum PSA, Gleason score, and uptake time of patients with [ 18 F]PSMA-1007 avid NSBLs to patients without [ 18 F]PSMA-1007 avid bone lesions. Finally, we analysed an SUVmax threshold to identify bone metastases using ROC curve analysis., Results: Ninety-four of 214 patients (43.9%) demonstrated at least one NSBL. No [ 18 F]PSMA-1007 avid NSBLs met criteria for a likely malignant or definitely malignant lesion after a median 15.8-month follow-up interval (11.9% definitely benign, 50.3% likely benign, and 37.7% equivocal). There were no statistically significant differences in serum PSA, Gleason score, and uptake time between patients with [ 18 F]PSMA-1007 avid NSBLs and those without [ 18 F]PSMA-1007 avid bone lesions. All NSBLs with adequate follow-up had SUVmax ≤ 11.1. The value of the highest SUVmax distinguished between NSBLs and definite prostate cancer bone metastases, whereby an SUVmax threshold of ≥ 7.2 maximized the Youden's index., Conclusion: [ 18 F]PSMA-1007 avid NSBLs rarely represent prostate cancer bone metastases. When identified in the absence of definite metastatic disease elsewhere, it is appropriate to classify those with SUVmax < 7.2 as likely benign. NSBLs with SUVmax 7.2-11.1 may be classified as equivocal or metastatic, with patient clinical risk factors, scan appearance, and potential management implications used to guide interpretation., (© 2021. Crown.)

Background: 99mTechnetium-HDP (HDP) bone scans differentiate transthyretin (ATTR) cardiac amyloid from other infiltrative myocardial diseases. These scans are not quantitative and are assessed by comparing myocardial uptake to bone. This study examined whether quantitative HDP SPECT/CT can discriminate individuals with cardiac ATTR from the population without this disease., Methods: HDP thoracic xSPECT/CT QUANT (xQUANT) was performed in 29 patients: ATTR cardiac amyloid ( n  = 6); AL cardiac amyloid ( n  = 1); other infiltrative myocardial disease ( n  = 4); no known infiltrative cardiac disease ( n  = 18). SUVmax measured within volumes of interest for whole heart, ascending aorta blood pool, and specific bones. HDP myocardial uptake calculated as whole heart minus blood pool., Results: The cardiac ATTR group had greater HDP myocardial uptake than those with no known infiltrative disease ( p  = 0.002). AL and other myocardial diseases had uptake indistinguishable from the group with no known infiltrative cardiac disease. The SUVmaxima were sufficiently similar between individuals without cardiac ATTR that a 99% reference interval for HDP uptake could be calculated, providing an upper limit cut point of SUVmax 1.2. Individuals with cardiac ATTR had SUVmax well above this cut point., Conclusion: Quantitative SPECT/CT can measure HDP myocardial uptake in individuals with normal hearts and those with cardiac ATTR without recourse to comparison with bone. It enables calculation of a reference interval for HDP myocardial uptake in the population without ATTR cardiac amyloid. Using this reference interval single individuals with cardiac ATTR can be accurately discriminated from the non-affected population. This technique uses a NIST traceable calibration source, potentially allowing development of multicentre clinical decision limits. Its role in disease management warrants further assessment., Competing Interests: The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Migrant families caring for family members with mild cognitive impairment (MCI) face considerable socioeconomic burden and isolation., Aim: To examine the cultural needs, beliefs and health seeking behaviours of migrant Turkish family member caregivers., Design: An ethnographic approach was used employing in depth interviews., Methods: Turkish caregivers residing in Melbourne, Australia were purposively sampled. Ten participants undertook face-to-face interviews in Turkish and English, followed by coding, transcription and thematic analysis., Results: Common themes were: (i) characteristics of MCI; (ii) care complicates our lives; (iii) beneficial coping strategies; (iv) adherence to cultural beliefs; (v) an uncertain future; (vi) interfacing with community health providers: need to understand Turkish culture (vii) need for long-term support. Migrant caregivers voiced undergoing considerable stress exacerbated by their cultural obligations., Conclusions: Establishing ethnically appropriate community support groups and advocating for a health workforce tier of representative migrant health care workers is recommended as a new role for community nurses.

Unlabelled: Synchrotron-based X-ray fluorescence microscopy (XFM) can localise chemical elements at a subcellular level. 99mTechnetium stannous (TcSn) colloid is taken up by phagocytes via a Complement Receptor 3 mediated phagocytic process. In the current study, XFM was used to examine the intracellular trafficking of TcSn colloid in neutrophils. XFM was performed on TcSn colloid, and neutrophils labelled with TcSn colloid, in whole blood. We developed a set of pixel by pixel analysis and mapping techniques incorporating cluster analysis that allowed us to differentiate neutrophils and artefactual contaminants, and we examined the changes in element distribution that accompany neutrophil phagocytosis of TcSn colloid. Sn became associated with half the neutrophils. Within cells, Sn colocalised with iron (Fe) and sulphur (S), and was negatively associated with calcium (Ca). Despite the high sensitivity of XFM, Tc was not detected. XFM can help clarify the intracellular processes that accompany neutrophil phagocytosis. The subcellular colocalisation of Sn with Fe is consistent with fusion of the colloid-containing phagosome with neutrophil granules. The association of Sn with S suggests that proteins rich in S-containing amino acids are present in the phagosome. The negative colocalisation with Ca indicates that ongoing maturation of the TcSn colloid phagosome is no longer calcium dependent one hour after phagocytosis., Electronic Supplementary Material: The online version of this article (doi:10.1007/s10867-011-9233-9) contains supplementary material, which is available to authorized users.

We report 2 cases demonstrating that localization of internal mammary (IM) sentinel lymph nodes with lymphoscintigraphy using peritumoral injection of Tc-99m antimony sulfide colloid, followed by resection using minimal access surgery, can reveal nodal metastatic disease in patients with clinically node-negative breast cancer when axillary sentinel nodes are not affected by metastatic disease. When this is found, it changes staging and can affect prognosis and treatment. These cases confirm that the technique used is sampling true sentinel IM nodes, that is nodes that receive direct lymph flow from the breast cancer, and confirm the importance of sampling IM sentinel lymph nodes. Unless techniques are used that are specifically designed to identify IM node drainage from the breast cancer site itself, with subsequent directed surgical removal of sentinel IM nodes, some patients with breast cancer will not be staged correctly.

Introduction: (99m)Technetium stannous colloid (TcSnC) is used in white cell scanning. It labels neutrophils and monocytes via phagocytosis, with uptake mediated by the phagocytic receptor CD11b/CD18 in neutrophils. Uptake of TcSnC is altered by gram-negative infection, possibly due to the endotoxin component lipopolysaccharide (LPS) or to cytokines released during infection (e.g., TNF-alpha and IFN-gamma). Endotoxemia and increased TNF-alpha levels also occur in inflammatory bowel disease. Another potential confounder in cell labeling is that sepsis patients may be treated with GM-CSF and G-CSF, which alter phagocytic cell function. This study aimed to determine how these factors affect TcSnC cellular uptake., Methods: Whole blood from six healthy volunteers was incubated with LPS, TNF-alpha, IFN-gamma, GM-CSF or G-CSF. Samples were then mixed with TcSnC. Blood was separated across density gradients and imaged using a gamma camera. Three radioactive count peaks were observed in each tube: free plasma activity, mononuclear cell uptake and neutrophil uptake., Results: Compared with controls, significant increases in mononuclear cell uptake were induced by LPS, TNF-alpha and GM-CSF stimulation. It was incidentally noted that exogenous estrogens appear to affect TcSnC labeling and may influence the neutrophil response to stimulation. Neutrophil uptake and plasma activity were not significantly affected. IFN-gamma and G-CSF had no significant effect., Conclusions: In whole blood, the effect of LPS on TcSnC monocyte uptake is different to its effect on neutrophils, consistent with previously reported differences in CD11b/CD18 expression. TNF-alpha response parallels LPS response. GM-CSF also increases TcSnC uptake by monocytes. These effects should be considered when using TcSnC for imaging purposes, as they will tend to increase monocyte labeling. Estrogens may also affect TcSnC labeling. Responses to IFN-gamma and G-CSF are consistent with previously reported effects of these cytokines on CD11b/CD18 expression.

Introduction: [(99m)Tc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming., Methods: We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent., Results: Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells., Conclusions: Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection.

Gram-negative infection alters phagocytic cell function; hence, it could affect phagocytic uptake of inorganic colloids by these cells. Neutrophil and monocyte uptake of technetium 99m stannous colloid (99mTc SnC) in whole blood was measured in 10 patients with gram-negative infection (Burkholderia pseudomallei) and 7 controls. Mean uptake per individual neutrophil was reduced in infection. Uptake per monocyte was not significantly different. Blood from six normal individuals was incubated with lysed B. pseudomallei and colloid, which showed reduced neutrophil uptake, but increased monocyte uptake. These results indicate that uptake of 99mTc SnC stannous colloid can be used to measure alteration in phagocytic cell function. They suggest that infection with B. pseudomallei is associated with reduced phagocytosis by individual neutrophils, possibly through toxic effects of bacterial products. This could have immunopathogenic consequences for this gram-negative infection and may explain why it responds to granulocyte colony-stimulating factor.

Melioidosis is an infectious disease that can present with multiple foci of disease involvement. Assessment of disease extent can be difficult, especially in musculoskeletal, visceral and soft tissue infection. This study examined the usefulness of white cell scans in this condition. 99mTc stannous colloid white cell scanning was performed in 21 patients with culture-proven melioidosis. Scan results were compared with clinical assessment and correlated with other forms of imaging. White cell scans demonstrated all but one of the clinically apparent sites of musculoskeletal, visceral and other soft tissue infection. Unsuspected disseminated soft tissue lesions were seen in two patients, including femoral node uptake in both, and these patients subsequently presented with relapsing musculoskeletal disease. Unsuspected musculoskeletal disease was found in one patient. Clinically suspected musculoskeletal disease was accurately excluded by white cell scan in another patient. The results of white cell scanning were also examined in disease of other viscera. Renal and prostatic disease were visualized. Unsuspected parotid involvement was found in two patients. Only one of two spinal lesions was visualized. Pulmonary disease was not necessarily associated with abnormal uptake. White cell scanning is a quick and effective way of assessing the extent of musculoskeletal, visceral and soft tissue disease in melioidosis.

1. The role of supra-brainstem structures in the ventilatory response to inhaled CO2 is unknown. The present study uses positron emission tomography (PET), with infusion of H2(15)O, to measure changes in relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during CO2-stimulated breathing (CO2-SB) in awake man. 2. Five male volunteers were scanned during CO2-SB (mean +/- S.E.M.; end-tidal PCO2, 50.3 +/- 1.7 mmHg; respiratory frequency, 16.4 +/- 2.7 min-1; tidal volume, 1.8 +/- 0.2 l). As control, scans were performed during 'passive' isocapnic (elevated fraction of inspired CO2) positive pressure ventilation (end-tidal PCO2, 38.4 +/- 1.0 mmHg; respiratory frequency, 15.5 +/- 2.2 min-1; tidal volume, 1.6 +/- 0.2 l). With CO2-SB, all subjects reported dyspnoea. 3. The anatomical locations of the increases in relative rCBF (CO2-SB versus control) were obtained using magnetic resonance imaging. 4. Group analysis identified neuronal activation within the upper brainstem, midbrain and hypothalamus, thalamus, hippocampus and parahippocampus, fusiform gyrus, cingulate area, insula, frontal cortex, temporo-occipital cortex and parietal cortex. No neuronal activation was seen within the primary motor cortex (at sites previously shown to be associated with volitional breathing). 5. These results suggest neuronal activation within the limbic system; this activation may be important in the sensory and/or motor respiratory responses to hypercapnia in awake man.

1. The primary objective of this study was to examine in man, how induced changes in global cerebral blood flow (gCBF) affected a regional cerebral blood flow (rCBF) increase resulting from a neural activation task (opening of eyes). A secondary objective was to quantify how such induced changes in gCBF were distributed between representative regions of either predominantly grey matter or white matter. 2. Positron emission tomography with intravenous infusion of H2(15)O, was used to measure gCBF in six normal males. Concomitant measures of rCBF were obtained in three different regions of interest (ROI): a representative area of predominantly grey matter, a representative area of predominantly white matter and an area of visual cortex. 3. Cerebral blood flow was altered by establishing steady-state changes in PCO2 at a near constant ventilation of approximately 30 l min-1. The mean PET,CO2 (+/- S.D.) levels (mmHg) that resulted were: low, 21.8 +/- 1.8; normal, 39.8 +/- 1.0, and high, 54.8 +/- 1.2. The normal and high levels were obtained by adding appropriate amounts of CO2 to the inspirate. The corresponding mean gCBF levels across all six subjects with eyes closed were: low, 24.2 +/- 4.6; normal, 37.2 +/- 3.9 and high, 66.8 +/- 7.6 ml min-1 dl-1. 4. Blood flow in grey matter (insular cortex) and white matter (centrum semiovale) at normal levels of PCO2 averaged 56.8 +/- 10.1 and 20.3 +/- 3.4 ml min dl-1 respectively. As PCO2 rose, the increase in rCBF to grey matter was approximately three times greater than that to white matter. 5. An activation state of eyes open in a brightly lit room was compared to a baseline state of eyes closed in a darkened room at the three levels of PCO2 (and hence at three levels of gCBF). Over the whole gCBF range a significant (P = 0.028) effect of increasing rCBF in the visual cortex ROI was found in response to opening the eyes; the effect of this activation on rCBF was not significantly dependent (P = 0.34) on the PCO2 (and hence gCBF) level. The effect of the activation on the rCBF was apparently 'additive' to the rise of rCBF associated with PCO2-related gCBF increase. 6. The results confirm the need to normalize for changes in gCBF during studies of rCBF in response to an activation protocol. They also provide support for the use of an 'additive' model to achieve such normalization provided that other cortical areas behave in a similar manner to that of the visual cortex.

1. Positron emission tomographic (PET) imaging of regional cerebral blood flow (rCBF), using a new 3-dimensional technique of data collection, was used to identify areas of neuronal activation associated with volitional inspiration and separately with volitional expiration in five normal male subjects. A comparison of the activated areas was also undertaken to isolate regions specific for one or other active task. 2. Scans were performed during intravenous infusion of H2(15)O under conditions of (a) volitional inspiration with passive expiration, (b) passive inspiration with volitional expiration and (c) passive inspiration with passive expiration. Four measurements in these three conditions were performed in each subject. Breathing pattern was well matched between conditions. 3. Regional increases in brain blood flow, due to increased neural activity associated with either active inspiration or active expiration, were derived using a pixel by pixel comparison of images obtained during the volitional and passive ventilation phases. Data were pooled from all runs in all subjects and were then processed to detect statistically significant (P < 0.05) increases in rCBF comparing active inspiration with passive inspiration and active expiration with passive expiration. 4. During active inspiration significant increases in rCBF were found bilaterally in the primary motor cortex dorsally just lateral to the vertex, in the supplementary motor area, in the right lateral pre-motor cortex and in the left ventrolateral thalamus. 5. In active expiration significant increases in rCBF were found in the right and left primary motor cortices dorsally just lateral to the vertex, the right and left primary motor cortices more ventrolaterally, the supplementary motor area, the right lateral pre-motor cortex, the ventrolateral thalamus bilaterally, and the cerebellum. 6. Using this modified and more sensitive PET technique, these findings essentially replicate those for volitional inspiration obtained in a previous study. For volitional expiration the areas activated are more extensive, but overlap with those involved in volitional inspiration. 7. The technique used has been successful in demonstrating the regions of the brain involved in the generation of volitional breathing, and probably in the volitional modulation of automatic breathing patterns such as would be required for the production of speech.

We have previously shown bilateral activation of motor pathways and the recruitment of additional motor areas in studies of groups of patients with recovery from motor stroke. We have now developed a new positron emission tomographic technique to measure the changes in regional cerebral blood flow elicited during a motor task in individual patients, relative to the cerebral activation found in normal subjects. The patterns of cerebral activation in each of 8 individual patients with capsular lesions of the pyramidal tract and complete recovery from hemiplegia are described by comparison with the pattern found in a representative sample of 10 normal subjects. We found a large ventral extension of the hand field of the contralateral (sensori)motor cortex in all patients with lesions of the posterior limb of the internal capsule. Greater activation than in normal subjects was found in variable combinations of the supplementary motor areas, the insula, the frontal operculum, and the parietal cortex. Structures belonging to motor pathways ipsilateral to the recovered limb were also more activated in the patients than in normal subjects. However, additional activation of the ipsilateral (sensori)motor cortex was only found in the 4 patients who exhibited associated movements of the unaffected hand when the recovered hand performed the motor task. We conclude that recovery from motor stroke due to striatocapsular damage is associated with individually different patterns of functional reorganization of the brain. These patterns are dependent on the site of the subcortical lesion and the somatotopic organization of the pyramidal tract, both of which may determine the precise potential for recovery of limb function following this type of brain injury.

Single photon emission computed tomography (SPECT) scanning with 99TcHMPAO (Ceretec) was used to demonstrate regional cerebral blood flow (rCBF) in sixteen patients with hemodynamically significant unilateral carotid stenosis. All patients were demonstrated by cerebral computed tomography to be without cerebral infarction. When dysautoregulation was induced by intravenous acetazolamide, eight patients demonstrated a perfusion defect ipsilateral to carotid stenosis. Repeat SPECT scanning with dysautoregulation following carotid endarterectomy showed improved or normal cerebral perfusion in seven of these patients. The results suggest that a hemodynamic mechanism for cerebral ischemic events, including transient ischemic attacks (TIA) may be more common than previously suspected. Carotid disobliteration usually improves ipsilateral cerebrovascular reserve in patients with a preoperative perfusion defect.

Technetium-HMPAO cerebral SPECT was performed interictally, immediately after an independent aura and ictally in a patient with complex partial seizures. Interictally there was a left inferior frontoparietal region of decreased perfusion. Ictally there were a number of foci of increased perfusion. The aura study showed focal hyperperfusion in the left frontal region and decreased perfusion in the adjacent cortex posteriorly, suggesting a zone of suppression. This may be the cause or effect of the nonprogression of the aura. The case raises the possibility that cerebral perfusion studies performed immediately after independent auras may localize seizure foci if ictal studies are nonfocal.

The mechanisms responsible for gallium uptake in chronic, non-infective, diffuse lung disease are not completely understood. This study attempted to clarify some of them. A lung/liver gallium index was calculated in 113 subjects, some normal and some with various interstitial lung diseases, predominantly those associated with connective tissue disease. The mean gallium index was significantly higher in the groups with active interstitial lung disease (5.7) and non-infective bronchiolitis (4.1) compared with non-smoking normals (3.0; P less than 0.05). To investigate the mechanisms responsible for gallium uptake, the gallium index was correlated with bronchoalveolar lavage findings, respiratory function tests and clinical features. Significant correlations (P less than 0.05) were found with age in non-smoking normals; lavage macrophages in smoking normals; age but no other parameter in bronchiolitis; lavage lymphocytes, lavage albumin and improvement in diffusion capacity for carbon monoxide in those with active interstitial lung disease. It is concluded that in normal smokers gallium uptake may be due to a macrophage-mediated process. Gallium uptake in active interstitial lung disease associated with connective tissue disease appears to be an immunological process in which transport and retention of gallium is associated with that of albumin.

Cerebral perfusion through stenosed internal carotid arteries is usually maintained by autoregulation. However, flow reserve may be reduced, suggesting hemodynamically significant stenosis, and such reduction should be improved by carotid endarterectomy. This concept was studied in 20 subjects with unilateral internal carotid artery stenosis (major stenosis greater than or equal to 70%, minor stenosis less than or equal to 50%). Thirteen had experienced recent transient ischemic attacks and seven had no definite focal symptoms. Subjects underwent Tc-HMPAO cerebral SPECT during acetazolamide dysautoregulation before and after internal carotid endarterectomy. Nine (45%) had perfusion defects that improved after surgery, suggesting surgery had improved cerebral flow reserve. Seven had defects that did not improve after surgery. Four had worsened or new defects after surgery, suggesting perioperative infarcts. The relatively large proportion of patients with improved cerebral blood flow reserve after surgery suggests that this technique may have a significant role to play in assessing which patients might benefit from carotid endarterectomy.

This study examined the role of radionuclide bone scanning in the early assessment of free autologous cancellous bone grafts in augmentation rhinoplasty and compared the failure rates of grafts taken from the calvaria and ilium. Twenty patients had three-phase bone scanning of the facial regions performed between 2 and 15 wk after rhinoplasty, and a comparison was made with the results of clinical assessment and X-ray findings 3 mo after surgery. Eleven patients had grafts taken from the calvaria and nine had iliac grafts. On lateral views, bone graft uptake of isotope, which was less than or equal to the adjacent soft tissue, was found in 2 out of 20 patients and this finding predicted subsequent graft failure as measured by clinical assessment and X-ray evidence of bone resorption. Both failures had grafts taken from the calvaria while none from the ilium failed. These failure rates, however, were not significantly different.