Preventive effect of continuous cisternal irrigation with magnesium sulfate solution on angiographic cerebral vasospasms associated with aneurysmal subarachnoid hemorrhages: a randomized controlled trial.

OBJECT Although cerebral vasospasm (CV) is one of the most important predictors for the outcome in patients with subarachnoid hemorrhage (SAH), no treatment has yet been established for this condition. This study investigated the efficacy of continuous direct infusion of magnesium sulfate (MgSO4) solution into the intrathecal cistern in patients with an aneurysmal SAH. METHODS An SAH caused by a ruptured aneurysm was identified on CT scans within 72 hours after SAH onset. All patients were treated by surgical clipping and randomized into 2 groups: a control group of patients undergoing a standard treatment and a magnesium (Mg) group of patients additionally undergoing continuous infusion of 5 mmol/L MgSO4 solution for 14 days. The Mg(2+) concentrations in serum and CSF were recorded daily. Neurological examinations were performed by intensive care clinicians. Delayed cerebral ischemia was monitored by CT or MRI. To assess the effect of the Mg treatment on CV, the CVs were graded on the basis of the relative degree of constriction visible on cerebral angiograms taken on Day 10 after the SAH, and transcranial Doppler ultrasonography was performed daily to measure blood flow velocity in the middle cerebral artery (MCA). Neurological outcomes and mortality rates were evaluated with the Glasgow Outcome Scale and modified Rankin Scale at 3 months after SAH onset. RESULTS Seventy-three patients admitted during the period of April 2008 to March 2013 were eligible and enrolled in this study. Three patients were excluded because of violation of protocol requirements. The 2 groups did not significantly differ in age, sex, World Federation of Neurosurgical Societies grade, or Fisher grade. In the Mg group, the Mg(2+) concentration in CSF gradually increased from Day 4 after initiation of the continuous MgSO4 intrathecal administration. No such increase was observed in the control group. No significant changes in the serum Mg(2+) levels were observed for 14 days, and no cardiovascular complications such as bradycardia or hypotension were observed in any of the patients. However, bradypnea was noted among patients in the Mg group. The Mg group had a significantly better CV grade than the control group (p < 0.05). Compared with the patients in the Mg group, those in the control group had a significantly elevated blood flow velocity in the MCA. Both groups were similar in the incidences of cerebral infarction, and the 2 groups also did not significantly differ in clinical outcomes. CONCLUSIONS Continuous cisternal irrigation with MgSO4 solution starting on Day 4 and continuing to Day 14 significantly inhibited CV in patients with aneurysmal SAH without severe cardiovascular complications. However, this improvement in CV neither reduced the incidence of delayed cerebral ischemia nor improved the functional outcomes in patients with SAH.

Posterior auricular artery-middle cerebral artery bypass: a rare superficial temporal artery variant with well-developed posterior auricular artery-case report.

The posterior auricular artery (PAA) is one of the branches of the external carotid artery, but is usually too small for use as a donor artery for middle cerebral artery (MCA) territory revascularization. An extremely unusual case of PAA-MCA anastomosis was performed in a patient requiring MCA territory revascularization because the superficial temporal artery (STA) parietal branch was absent and the PAA was large enough. A 65-year-old man developed mild motor weakness in the right extremities caused by multiple small infarctions. Single photon emission computed tomography (CT) revealed deterioration of the vascular reserve capacity in the left MCA area. Cerebral angiography showed severe stenosis in the C2 portion of the left internal carotid artery, absence of the parietal branch of the left STA, and a well-developed PAA extending to the parietal area. The patient underwent STA (frontal branch)-MCA and PAA-MCA double anastomosis, and has suffered no stroke or transient ischemic attack. The STA with no bifurcation is known as a rare variation. The PAA also occurs with size variations but well-developed PAA is thought to be extremely rare. PAA can be used as a donor artery for MCA territory revascularization if the vessel size is suitable. Preoperative evaluation of the anatomy is mandatory for harvesting the arteries.

Trigeminal neuralgia caused by venous angioma: case report.

A 34-year-old female presented with trigeminal neuralgia caused by a venous malformation in the right cerebello-pontine region. Computed tomography and magnetic resonance imaging demonstrated the abnormal draining veins from the venous malformation. The dilated vessels extended around the trigeminal nerve and compressed the root entry zone. Microvascular decompression (MVD) was performed, and her trigeminal neuralgia was completely relieved without neurological deficits. The offending vessel in most cases of trigeminal neuralgia is an arterial branch. Veins may also be associated with trigeminal neuralgia. The present rare case shows that MVD may be useful for the treatment of trigeminal neuralgia associated with venous malformation. Good outcome depends on decompression of the root entry zone without injury to the vessel. Surgical injury in this region can cause severe neurological deficits. Several treatment options should be prepared for the surgery, such as MVD or rhizotomy.

Effect of intrathecal magnesium sulfate solution injection via a microcatheter in the cisterna magna on cerebral vasospasm in the canine subarachnoid haemorrhage model.

OBJECTIVE: To evaluate intracisternal injection of magnesium sulfate (MgSO(4)) solution via a lumbar catheter for the treatment of cerebral vasospasm in the canine subarachnoid haemorrhage (SAH) model. MATERIALS AND METHODS: SAH was induced in 7 beagle dogs using the dual haemorrhage model. Vertebral angiography was repeated on Day 1 (before SAH), and on Day 7 (during cerebral vasospasm) before and 1.5 hours after injection of 0.5 mL/kg of 15 mmol/L MgSO(4) in Ringer solution via the tip of a microcatheter placed in the cisterna magna from the lumbar spine. RESULTS: After injection of MgSO(4) solution, the cerebrospinal fluid magnesium ion concentration significantly increased to 3.89 ± 0.97 mEq/L (P < 0.01) from the baseline value (1.49 ± 0.07 mEq/L). The arterial diameters of the basilar artery (BA), vertebral artery (VA), and superior cerebral artery (SCA) on Day 1 were 1.26 ± 0.19 mm, 1.10 ± 0.13 mm, and 0.74 ± 0.21 mm, respectively. On Day 7 before injection, the arterial diameters of the BA, VA, and SCA significantly decreased to 0.75 ± 0.27 mm, 0.74 ± 0.25 mm, and 0.36 ± 0.21 mm, respectively (P < 0.01), due to vasospasm, and were significantly increased to 0.91 ± 0.27 mm (P < 0.01), 0.91 ± 0.31 mm (P < 0.05), and 0.54 ± 0.14 mm (P < 0.01), respectively, after intracisternal injection of MgSO(4) solution. CONCLUSIONS: Intracisternal MgSO(4) therapy using a microcatheter from the lumbar spine may be effective against vasospasm in the clinical setting of endovascular treatment of ruptured aneurysm.

Surgical simulation of cerebral revascularization via skull base approaches in the posterior circulation using three-dimensional skull model with artificial brain and blood vessels.

Posterior circulation revascularization is a challenging technique because microanastomosis must be performed in deep locations. A reproducible simulation model is proposed for training. The prototype three-dimensional skull model with artificial brain was used. The mesencephalic segment of superior cerebellar artery (SCA) and the caudal loop of the posterior inferior cerebellar artery (PICA) were made from artificial blood vessels and glued on the brain. The skull model was drilled to perform the presigmoid transpetrosal approach and then superficial temporal artery-SCA anastomosis was performed under the operating microscope. The skull model was also drilled to perform the far lateral approach and then occipital artery-PICA anastomosis was performed. The skull model with artificial brain and arteries allows simulation and training in the surgical techniques of posterior circulation revascularization with skull base approaches.

Possible neuro-Sweet disease mimicking brain tumor in the medulla oblongata--case report.

A 62-year-old male presented with a rare case of possible neuro-Sweet Disease (NSD) mimicking brain tumor in the medulla oblongata, manifesting as numbness in the bilateral upper and lower extremities, gait disturbance, dysarthria, and swallowing disturbance which gradually deteriorated over 3 months. Magnetic resonance imaging showed a mass lesion in the medulla oblongata, extending to the upper cervical cord with rim enhancement by gadolinium. The preoperative diagnosis was brain tumor, such as glioma, or inflammatory disease. His neurological symptoms gradually deteriorated, so biopsy was performed through the midline suboccipital approach. Histological examination showed infiltration of inflammatory cells, mainly lymphocytes and macrophages. Human leukocyte antigen typing showed Cw1 and B54 which strongly suggested possible NSD. Steroid pulse therapy was started after surgery and the clinical symptoms improved. Neurosurgeons should be aware of inflammatory disorders such as NSD mimicking brain tumor.

Use of [18F]fluorodeoxyglucose and the ATLAS small animal PET scanner to examine cerebral functional activation by whisker stimulation in unanesthetized rats.

PURPOSE: Stroking the whiskers of a rat is known to increase cerebral blood flow and glucose utilization in the somatosensory cortex. We sought to determine whether this activation could be detected with small animal PET and 2-[F]fluoro-2-deoxyglucose ([F]FDG). METHODS: Awake rats were coinjected with [F]FDG and [C]deoxyglucose ([C]DG), and during the uptake of the tracers, five, 10, or 15 whiskers on one side of the face were continuously stimulated. At the end of uptake, the animal was killed and imaged with the Advanced Technology Laboratory Animal Scanner small animal PET scanner. Carbon-14 autoradiography was then performed on brain sections obtained from each animal, and increases in tracer uptake in the somatosensory cortex were compared with those determined with PET. RESULTS: Both methods showed increases in [F]FDG and [C]DG uptake in the somatosensory cortex in response to the stimulation of as few as five whiskers. However, the magnitude of activation determined from the PET images was less than that from autoradiography due to the lower spatial resolution of the PET scanner. CONCLUSION: Advanced Technology Laboratory Animal Scanner small animal PET imaging with [F]FDG can be used to assess neuronal functional activity in vivo.

Temporal profile of the effects of intracisternal injection of magnesium sulfate solution on vasodilation of spastic cerebral arteries in the canine SAH model.

PURPOSE: the temporal profiles of the effects of intracisternal injection of magnesium sulfate (MgSO(4)) on vasodilation and cerebrospinal fluid (CSF) magnesium ion (Mg(2+)) concentration were investigated in the canine subarachnoid hemorrhage (SAH) model. METHOD: cerebral vasospasm was induced using the two-hemorrhage model in seven female beagles. On day 7, 0.5 ml/kg of 15 mmol/l MgSO(4) in Ringer solution was injected into the cerebellomedullary cistern. Angiography was performed on day 1 (before SAH), and before and 1, 3, and 6 h after the intracisternal injection on day 7. CSF Mg(2+) was measured at the same time. RESULTS: the diameters of the basilar artery (BA), vertebral artery (VA), and superior cerebellar artery (SCA) before the intracisternal injection on day 7 were 0.59 ± 0.15, 0.41 ± 0.17, and 0.35 ± 0.17 mm, respectively, and were significantly decreased (p < 0.01) compared with the baseline diameters on day 1. The BA diameters at 1 h (0.74 ± 0.16 mm) and 3 h (0.73 ± 0.13 mm), the VA diameter at 1 h (0.64 ± 0.14 mm), and the SCA diameter at 3 h (0.54 ± 0.08 mm) after the injection were significantly increased (p < 0.05). The CSF Mg(2+) concentration was significantly increased (p < 0.01) at 1 h (3.59 ± 0.76 mEq/l) and 3 h (2.00 ± 0.31 mEq/l) after the injection compared with the baseline value (1.35 ± 0.23 mEq/l). CONCLUSIONS: the reversible effect of intracisternal MgSO(4) solution injection on the spastic artery depends on maintenance of the optimal CSF Mg(2+) concentration.

Optimal cerebrospinal fluid magnesium ion concentration for vasodilatory effect and duration after intracisternal injection of magnesium sulfate solution in a canine subarachnoid hemorrhage model.

OBJECT: The optimal CSF Mg(++) concentration for vasodilation of spastic cerebral arteries after subarachnoid hemorrhage (SAH) and its duration are unknown. The temporal profile of the vasodilatory effect and optimal CSF Mg(++) concentration after the intracisternal injection of MgSO(4) solution were investigated in an SAH model in canines. METHODS: Cerebral vasospasm was induced by experimental SAH using a 2-hemorrhage model in 26 female beagles. On Day 7, 0.5 ml/kg of 15, 10, 5, or 0 mmol/L MgSO(4) in Ringer solution was injected into the cerebellomedullary cistern. Angiography was performed on Day 1 (before SAH) and before and 1, 3, and 6 hours after the intracisternal injection on Day 7 to measure arterial diameters of the basilar artery (BA), superior cerebellar artery (SCA), and vertebral artery (VA). Cerebrospinal fluid Mg(++) was also measured at the same time. RESULTS: Arterial diameters of the BA, SCA, and VA were significantly decreased by vasospasm on Day 7. Arterial diameter ratios (ratio of arterial diameter after MgSO(4) injection to diameter before injection on Day 7) of the BA and SCA at 1 and 3 hours after and the VA at 1 hour after intracisternal injection of the MgSO(4) solution were positively correlated with the CSF Mg(++) concentration. All arterial diameter ratios, except 1 point of the SCA, exceeded 1 if the CSF Mg(++) concentration was > 3 mEq/L at 1 hour after injection. Animals with CSF Mg(++) concentrations > 3 mEq/L at 1 hour after injection (11 dogs) showed significantly increased arterial diameters of the BA at 1 and 3 hours after and of the SCA and VA at 1, 3, and 6 hours after injection, as compared with the diameters before injection. The CSF Mg(++) concentration significantly increased at 1 hour (3.73 ± 0.69 mEq/L, p < 0.01) and 3 hours (2.05 ± 0.35 mEq/L, p < 0.01) after the intracisternal injection as compared with the baseline value (1.41 ± 0.20 mEq/L). CONCLUSIONS: The reversible effect of an intracisternal injection of MgSO(4) solution on the spastic artery requires CSF Mg(++) concentrations > 3 mEq/L. The vasodilatory effect continues for 3-6 hours after injection. These results suggest that the continuous infusion or intermittent intracisternal injection of MgSO(4) is needed to maintain the optimal CSF Mg(++) concentration and constantly ameliorate cerebral vasospasm.

Efficacy of low-dose tissue-plasminogen activator intracisternal administration for the prevention of cerebral vasospasm after subarachnoid hemorrhage.

BACKGROUND: Vasospasm is one of the important factors associated with the functional prognosis after subarachnoid hemorrhage (SAH). Intracisternal administration of thrombolytic agents to dissolve subarachnoid clots may be responsible for bleeding complications. The efficacy and safety of cisternal irrigation therapy using low-dose tissue plasminogen activator were evaluated. METHODS: Sixty patients with SAH were treated by surgical clipping, and randomly divided into three groups: 1) the control group (n = 20) treated only with baseline treatment; 2) the intermittent group (n = 20) received intermittent administration of clotlysis agent (tisokinase 960,000 IU); and 3) the continuous group (n = 20) received continuous irrigation using pH-adjusted lactate Ringer's solution containing tisokinase (96 IU/mL) infused at 20 mL/hr for 48 hours. The clearance of subarachnoid clots was measured by laboratory examinations and postoperative computed tomography. Ischemia-related vasospasm was evaluated by neurological status and computed tomography. Neurological outcome was evaluated by the modified Rankin scale at 3 months after onset. RESULTS: The subarachnoid clot was efficiently and significantly removed without major complication in the intermittent and continuous groups (P < 0.05). The incidence of ischemic lesion in the intermittent group was significantly lower than in the control group (P < 0.05). The intermittent group had significantly better neurological outcome than the control group (P < 0.05). CONCLUSIONS: Cisternal irrigation therapy using low-dose tissue plasminogen activator is effective and safe. Intermittent injection is most effective and may decrease the risk of symptomatic vasospasm in patients with SAH.

Development of artificial cranial base model with soft tissues for practical education: technical note.

OBJECTIVE: Improved educational tools for anatomic understanding and surgical simulation of the cranial base are needed because of the limited opportunities for cadaver dissection. A 3-dimensional cranial base model with retractable artificial dura mater is essential to simulate the epidural cranial base approach. METHODS: We developed our 3-dimensional cranial base model with artificial dura mater, venous sinuses, cavernous sinus, internal carotid artery, and cranial nerves, and the extradural temporopolar approach was simulated using this new model. INSTRUMENTATION: This model can be dissected with a surgical drill because of the artificial bone material. The periosteal dura was reconstructed in the medial wall of the cavernous sinus, periorbita, and periosteal bridge in the superior orbital fissure with yellow silicone. The meningeal dura was made with brown silicone. The single-layer dura mater could be dissected from the bone surface and retracted with a surgical spatula. RESULTS: Extradural drilling of the superior orbital fissure and opening of the optic canal were similar to actual surgery. Extradural anterior clinoidectomy was performed via the extradural space by retracting the artificial dura mater. The artificial dura propria of the lateral wall in the cavernous sinus was successfully peeled from the artificial cranial nerves to complete the extradural temporopolar approach. CONCLUSION: The improved 3-dimensional cranial base model provides a useful educational tool for the anatomic understanding and surgical simulation of extradural cranial base surgery.

[Comparison of the far lateral approach, transcondylar fossa approach, and transcondylar approach using a three-dimensional skull base model with artificial vertebral artery].

The far lateral approach, transcondylar fossa approach, and transcondylar approach are widely accepted as basic suboccipital lateral skull base techniques to treat various pathologies located in the lateral to anterior regions of the cervico-medullary junction. Surgical simulations were performed to evaluate the differences between these techniques using a three-dimensional dissectable skull base model with an artificial vertebral artery. The far lateral approach provided space around the intradural vertebral artery at the level of the jugular foramen. The transcondylar fossa approach allowed better visualization of the vertebral artery at the level between the jugular foramen and the hypoglossal canal. The transcondylar approach did not offer significantly better visualization of the vertebral artery compared with the transcondylar fossa approach except at the level below the hypoglossal canal. However, the transcondylar approach offered more extensive removal of the jugular tubercle than the transcondylar fossa approach because the removed occipital condyle, including the atlanto-occipital joint provided space for introduction of a surgical drill into the anterior part of this bony protuberance. Evaluation using the dissectable skull base model clearly demonstrated the differences in the surgical exposures of the intradural vertebral artery provided by these skull base approaches.

Malignant transformation 20 years after partial removal of intracranial epidermoid cyst--case report.

A 74-year-old woman presented with malignant progression of remnant epidermoid cyst manifesting as sudden onset of right ptosis and double vision. She had right oculomotor nerve paresis. She had a history of surgery for right cerebellopontine angle epidermoid cyst 20 years previously. T(1)-weighted magnetic resonance (MR) imaging demonstrated a hypointense mass lesion in the right cerebellopontine angle and basal cistern, and an isointense mass in the right paraclinoid region which was strongly enhanced. Diffusion-weighted MR imaging showed hyperintense areas in the right cerebellopontine angle, ambient cistern, and basal cistern, and the paraclinoid mass as hypointense. Surgery was performed using Dolenc's approach. Histological examination revealed that the paraclinoid tumor adjacent to the epidermoid tumor remnant was malignant transformation of epidermoid cyst into squamous cell carcinoma. She was treated with 46 Gy linac radiotherapy. She has been without tumor recurrence for 17 months. Malignant change of epidermoid cyst is extremely rare, but rapid progress of the symptoms suggests malignant transformation. MR imaging with gadolinium is useful for diagnosis.

Surgical Simulation of Extradural Anterior Clinoidectomy through the Trans-superior Orbital Fissure Approach Using a Dissectable Three-dimensional Skull Base Model with Artificial Cavernous Sinus.

Extradural anterior clinoidectomy via the trans-superior orbital fissure (SOF) approach can provide extensive exposure of the anterior clinoid process and safe drilling under direct view. This technique requires peeling of the dura propria of the temporal lobe from the lateral wall of the SOF. Therefore, cadaveric dissection is mandatory to acquire surgical technique. However, chances for cadaveric dissection are limited. We propose modification of our three-dimensional (3-D) skull base model made from surgically dissectable artificial bone with artificial cavernous sinus including multiple membranous layers and neurovascular structures to simulate extradural anterior clinoidectomy via the trans-SOF approach. The 3-D skull base model precisely reproduced the dura propria of the temporal lobe, periosteal bridge, and inner reticular layer in the cavernous sinus and SOF using silicone and varnish. The cranial nerves and blood vessels were made from rubber fibers and vinyl tube. Simulation of extradural anterior clinoidectomy via the trans-SOF approach could be performed on the model using a high-speed drill under the operating microscope. The steps of reconstruction of the skull base model and dissection promote clear understanding of the 3-D anatomy and techniques of extradural anterior clinoidectomy via the trans-SOF approach.

Initial clinical experience of vasodilatory effect of intra-cisternal infusion of magnesium sulfate for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

The vasodilatory effect of intra-cisternal infusion of magnesium sulfate solution was evaluated in 10 patients with symptomatic vasospasm after aneurysmal subarachnoid hemorrhage (SAH) who underwent early clipping surgery. Cisternal drainage was installed in the prepontine and/or sylvian fissures. Carotid angiography was performed immediately after the onset of symptomatic vasospasm, then intra-cisternal infusion of 15 mmol/l magnesium sulfate in Ringer solution was started at 20 ml/hr and continued until day 14. Irrigation was performed from the cisternal tube (inlet) to the spinal drainage (outlet). The cerebrospinal fluid magnesium ion concentration (1.2 +/- 0.2 mEq/l) significantly increased after the infusion therapy (6.0 +/- 1.7 mEq/l, p < 0.001). Repeat angiography showed vasodilatory effect on the spastic cerebral arteries at 3 hours after the infusion, especially in the arteries near to the site of cisternal drainage placement. The magnesium infusion also caused decreased mean arterial blood velocity in the spastic arteries in 6 of the 7 measured patients (162 +/- 38 cm/sec to 114 +/- 42 cm/sec, p < 0.001). Finally, 5 of the 10 patients achieved good recovery, 1 patient had moderate disability, 1 patient became severely disabled due to meningitis, and 3 patients were vegetative or dead, due to failure of magnesium irrigation in 1 patient and advanced age in the other 2 (more than 80 years old). This preliminary study indicates that intra-cisternal infusion of magnesium sulfate solution has vasodilatory effect on the spastic cerebral arteries after aneurysmal SAH.

Developmental disruption of serotonin transporter function impairs cerebral responses to whisker stimulation in mice.

There is growing evidence that serotonin (5-hydroxtryptamine, 5-HT) has major influences on brain development in mammals. Genetic and pharmacological disruption of 5-HT signaling during early postnatal development in rodents causes neuroanatomical cortical abnormalities, including malformations in the somatosensory cortex. Possible functional consequences of this developmental perturbation by 5-HT are not yet understood. We have examined the effects of deletion of the 5-HT transporter (5-HTT) gene on somatosensory responses to sensory stimulation in mice. Local cerebral glucose utilization (lCMR(glc)) was measured by the quantitative 2-deoxy[(14)C]glucose method during unilateral whisker stimulation in awake adult mice. lCMR(glc) was increased by stimulation but to a markedly lesser extent in 5-HTT(-/-) mice than in 5-HTT(+/+) controls in each of four major stations in the whisker-to-barrel cortex pathway (the spinal and principal sensory trigeminal nuclei, the ventral posteromedial thalamic nucleus, and the barrel region of the somatosensory cortex). Lowering brain 5-HT levels by administration of the selective tryptophan hydroxylase inhibitor p-chlorophenylalanine on postnatal days 0 and 1 restored the metabolic responses to functional activation in the whisker-to-barrel cortex pathway in adult 5-HTT(-/-) mice. These results indicate that functional deficits in this pathway in 5-HTT(-/-) mice may be due to excessive postnatal 5-HT activity. With or without postnatal p-chlorophenylalanine treatment, 5-HTT(-/-) mice exhibited lower resting (unstimulated) lCMR(glc) than did 5-HTT(+/+) controls in the whisker-to-barrel cortex pathway and throughout the brain. These findings have implications for understanding the potential long-term consequences of genetic and pharmacological disruption of 5-HT neurotransmission on cerebral functions during critical periods of postnatal development.

Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography.

UNLABELLED: The purpose of this study was to evaluate the feasibility of absolute quantification of regional cerebral glucose utilization (rCMR(glc)) in mice by use of (18)F-FDG and a small animal PET scanner. rCMR(glc) determined with (18)F-FDG PET was compared with values determined simultaneously by the autoradiographic 2-(14)C-DG method. In addition, we compared the rCMR(glc) values under isoflurane, ketamine and xylazine anesthesia, and awake states. METHODS: Immediately after injection of (18)F-FDG and 2-(14)C-DG into mice, timed arterial samples were drawn over 45 min to determine the time courses of (18)F-FDG and 2-(14)C-DG. Animals were euthanized at 45 min and their brain was imaged with the PET scanner. The brains were then processed for 2-(14)C-DG autoradiography. Regions of interest were manually placed over cortical regions on corresponding coronal (18)F-FDG PET and 2-(14)C-DG autoradiographic images. rCMR(glc) values were calculated for both tracers by the autoradiographic 2-(14)C-DG method with modifications for the different rate and lumped constants for the 2 tracers. RESULTS: Average rCMR(glc) values in cerebral cortex with (18)F-FDG PET under normoglycemic conditions (isoflurane and awake) were generally lower (by 8.3%) but strongly correlated with those of 2-(14)C-DG (r(2) = 0.95). On the other hand, under hyperglycemic conditions (ketamine/xylazine) average cortical rCMR(glc) values with (18)F-FDG PET were higher (by 17.3%) than those with 2-(14)C-DG. Values for rCMR(glc) and uptake (percentage injected dose per gram [%ID/g]) with (18)F-FDG PET were significantly lower under both isoflurane and ketamine/xylazine anesthesia than in the awake mice. However, the reductions of rCMR(glc) were markedly greater under isoflurane (by 57%) than under ketamine and xylazine (by 19%), whereas more marked reductions of %ID/g were observed with ketamine/xylazine (by 54%) than with isoflurane (by 37%). These reverse differences between isoflurane and ketamine/xylazine may be due to competitive effect of (18)F-FDG and glucose uptake to the brain under hyperglycemia. CONCLUSION: We were able to obtain accurate absolute quantification of rCMR(glc) with mouse (18)F-FDG PET imaging as confirmed by concurrent use of the autoradiographic 2-(14)C-DG method. Underestimation of rCMR(glc) by (18)F-FDG in normoglycemic conditions may be due to partial-volume effects. Computation of rCMR(glc) from (18)F-FDG data in hyperglycemic animals may require, however, alternative rate and lumped constants for (18)F-FDG.

Cardiac glucose utilization in mice with mutated alpha- and beta-thyroid hormone receptors.

Abnormal thyroid function is usually associated with altered cardiac function. Mutations in the thyroid hormone (TH)-binding region of the TH beta-receptor (TRbeta) that eliminate its TH-binding ability lead to the thyroid hormone resistance syndrome (RTH) in humans, which is characterized by high blood TH levels, goiter, hyperactivity, and tachycardia. Mice with "knock-in" mutations in the TH alpha-receptor (TRalpha) or TRbeta that remove their TH-binding ability have been developed, and those with the mutated TRbeta (TRbeta(PV/PV)) appear to provide a model for RTH. These two types of mutants show different effects on cerebral energy metabolism, e.g., negligible change in glucose utilization (CMR(Glc)) in TRbeta(PV/PV) mice and markedly reduced CMR(Glc), like that found in cretinous rats, in the mice (TRalpha(PV/+)) with the knock-in mutation of the TRalpha gene. Studies in knockout mice have indicated that the TRalpha may also influence heart rate. Because mutations in both receptor genes appear to affect some parameters of cardiac function and because cardiac functional activity and energy metabolism are linked, we measured heart glucose utilization (HMR(Glc)) in both the TRbeta(PV/PV) and TRalpha(PV/+) mutants. Compared with values in normal wild-type mice, HMR(Glc) was reduced (-77 to -95%) in TRalpha(PV/+) mutants and increased (87 to 340%) in TRbeta(PV/PV) mutants, the degree depending on the region of the heart. Thus the TRalpha(PV/+) and TRbeta(PV/PV) mutations lead, respectively, to opposite effects on energy metabolism in the heart that are consistent with the bradycardia seen in hypothyroidism and the tachycardia associated with hyperthyroidism and RTH.

Measurement of cerebral glucose metabolic rates in the anesthetized rat by dynamic scanning with 18F-FDG, the ATLAS small animal PET scanner, and arterial blood sampling.

UNLABELLED: Rodent models and genetically altered mice have recently become available to study many human diseases. A sensitive and accurate PET scanner for small animals would be useful to evaluate treatment of these diseases in rodent models. To examine the feasibility of performing quantitative PET studies, we performed dynamic scans with arterial blood sampling in anesthetized rats with the ATLAS (Advanced Technology Laboratory Animal Scanner) small animal PET scanner developed at the National Institutes of Health and (18)F-FDG and compared activities determined by PET scanning with those obtained by direct tissue sampling. METHODS: Dynamic PET scans after a bolus of approximately 48 MBq (1.3 mCi) (18)F-FDG were performed in rats anesthetized with isoflurane. Arterial blood sampling was performed throughout the scanning period. At 60 min the rat was killed, and the brain was rapidly removed and dissected into 5 structures (thalamus [TH], cortex [CX], brain stem [BS], cerebellum [CB], and half brain). Activity in the tissue samples was compared with the mean activity of the last 5 min of calibrated PET data. RESULTS: Plasma activity peaked at approximately 0.2 min and then cleared rapidly. Brain activity initially rose rapidly; the rate of increase then progressively slowed until activity was approximately constant between 30 and 60 min. Recovery coefficients (MBq/mL in PET images)/(MBq/mL in tissue samples) were 0.99 +/- 0.04, 0.90 +/- 0.19, 1.01 +/- 0.24, 0.84 +/- 0.05, and 1.01 +/- 0.17, respectively, in TH, CX, BS, CB, and half brain (mean +/- SD, n = 6-9). Cerebral glucose utilization determined by Patlak analyses of PET data measured 30-60 min after injection of (18)F-FDG was 31.7 +/- 5.2, 23.9 +/- 4.8, 29.9 +/- 5.0, 39.3 +/- 7.3, and 28.1 +/- 4.6 micro mol/100 g/min (mean +/- SD, n = 9) in TH, CX, BS, CB, and whole brain, respectively. These results are consistent with a previous (14)C-deoxyglucose study of the isoflurane-anesthetized rat. CONCLUSION: Expected values for glucose metabolic rates and recovery coefficients near unity suggest that quantitatively accurate dynamic (18)F-FDG brain imaging can be performed in the rat with arterial blood sampling and the ATLAS small animal PET scanner.