Comparative study of interictal PET and ictal SPECT in complex partial seizures.

OBJECTIVE: To compare the sensitivity of ictal 99mTc-HMPAO single photon emission computed tomography (SPECT) with interictal 18F-fluoro-deoxyglucose positron emission tomography (PET) in localization of the epileptogenic focus in patients with medically intractable complex partial seizures (MI-CPS). MATERIAL AND METHODS: Retrospective analysis was performed on patients with MI-CPS who underwent anterior temporal lobectomy from January 1993 onwards when PET became available to us for clinical studies at the Indiana University Medical Center. There were 38 female and 29 male patients (total = 67) with MI-CPS, 10 to 55.5 years of age (mean 31) and duration of their epilepsy from 1-46 years (mean 21). Interictal PET was evaluated for evidence of focal hypometabolism and ictal SPECT for focal perfusion abnormality (hyperperfusion or hypoperfusion) by visual analysis. RESULTS: Both ictal SPECT and interictal FDG-PET studies were obtained in 36 patients with MI-CPS. PET showed definite hypometabolism in 30 and questionable hypometabolism in an additional two patients. Ictal SPECT correctly localized the seizure focus in 27 patients by demonstrating ictal hyperperfusion whereas in one the hyperperfusion was falsely localized. In an additional seven patients the ictal SPECT provided probable localization by demonstrating ictal hypoperfusion in the appropriate temporal lobe. The sensitivity of ictal SPECT and interictal PET was 34/36 and 32/36, respectively, the difference was not statistically significant (chi 2y = 0.18, DF = 1, P = 0.67). In six of the 36 patients the two tests were complementary to each other in providing localizing information. CONCLUSION: Ictal SPECT and interictal PET are equally sensitive and reliable techniques in localizing the epileptogenic focus in patients with MI-CPS. They play a critical role in providing localization in MRI negative patients allowing surgical resection to be undertaken in many without additional invasive electrographic monitoring.

Defibrillation shocks over epicardial patches produce sympathetic neural dysfunction in man.

INTRODUCTION: The purpose of this study was to determine the effect of direct current (DC) shocks on cardiac sympathetic innervation in humans using I-123-metaiodobenzylguanidine (MIBG) scintigraphy. Decreased efferent sympathetic neural function has been demonstrated following > 10-J DC shocks delivered through epicardial patch electrodes in dogs. To evaluate the effect of DC shocks on cardiac sympathetic innervation in humans, we performed MIBG scintigraphy in 11 patients (ages 46 to 75 years) prior to and after receiving shocks from an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: This study was performed during an ICD generator change in 7 patients with epicardial patch electrodes and at the time of initial ICD implantation in 4 patients: 2 with epicardial patch electrodes, and 2 with a transvenous ICD system. All patients had spontaneous and inducible ventricular tachycardia. Prior to ICD implantation and remote from any cardioversions or shocks, baseline MIBG and thallium-201 scintigraphy were performed. Repeat MIBG scintigraphy was performed after delivery of ICD shocks and compared with the baseline scans to determine the effect of the shock on sympathetic neural function. The baseline scans revealed focal areas of reduced MIBG uptake in areas of thallium perfusion defects in all patients except the patient without structural heart disease whose scans were normal. Postshock, patients with epicardial patch electrodes who received at least one 24-J shock and had the postshock MIBG scan performed within 4 hours demonstrated no cardiac uptake of MIBG. Two patients with epicardial patch electrodes had no change in the postshock MIBG scans: 1 had a maximal shock of 20 J, and the other had the postshock scan delayed for 11 hours. The 2 patients with a transvenous lead system demonstrated no change in the postshock MIBG scan when compared with baseline. CONCLUSIONS: This study demonstrates that following DC shocks delivered over epicardial patch electrodes, there is diffuse reduction in MIBG uptake that probably represents cardiac sympathetic neural dysfunction that appears to be transient. Sympathetic function does not appear to be affected by shocks delivered over a transvenous lead system.

Direct comparison of fluorine-18-FDG SPECT, fluorine-18-FDG PET and rest thallium-201 SPECT for detection of myocardial viability.

UNLABELLED: Twenty consecutive patients were evaluated for presumptive myocardial viability using rest TI-SPECT, FDG-PET and FDG-SPECT. The FDG studies were performed after rest TI-SPECT to guide intervention or medical management. METHODS: Twenty patients with proven coronary artery disease, either known or suspected to have previous myocardial infarction and persistent perfusion defects shown by rest reinjection TI-SPECT, underwent FDG-PET and subsequent FDG-SPECT with a three-detector SPECT camera. FDG-PET and SPECT images were compared by five observers to determine if any fixed thallium segments were visualized by either FDG imaging method. RESULTS: Thirteen of 60 fixed segments were shown probably viable by FDG-SPECT (8 of 20 patients) and 14 of 60 by FDG PET (7 of 20 patients). Two patients had fixed thallium segments found probably viable with FDG by SPECT alone and one by PET alone. CONCLUSION: FDG is shown to provide additional information about myocardial viability. Both SPECT, using a three-detector camera, and PET with a specialized instrument are equally effective for imaging FDG in this application.

Regional cardiac sympathetic denervation in patients with ventricular tachycardia in the absence of coronary artery disease.

OBJECTIVES: The aim of this study was to determine whether patients with ventricular arrhythmias in the absence of coronary artery disease also have abnormalities in sympathetic innervation. BACKGROUND: We have previously shown by cardiac sympathetic scintigraphy using iodine-123-metaiodobenzylguanidine (I-123-MIBG) that patients with ventricular tachycardia after myocardial infarction have regional cardiac sympathetic denervation. It is not known whether patients with ventricular tachycardia in the absence of coronary artery disease also have regional cardiac sympathetic denervation. METHODS: We performed cardiac I-123-MIBG and thallium-201 single-photon emission computed tomographic (SPECT) scans at rest in 18 patients (mean age 47 +/- 18 years) with cardiomyopathy (n = 6), left ventricular hypertrophy (n = 1), valvular disease (n = 2) or a structurally normal heart (n = 9) who presented with monomorphic (n = 15) or polymorphic (n = 3) ventricular tachycardia. These scans were compared with scans in 12 control patients without ventricular tachycardia (mean age 30 +/- 17 years) who had cardiomyopathy (n = 3) or a structurally normal heart (n = 9). Cardiac sympathetic denervation was defined as myocardial areas having thallium uptake with reduced or absent I-123-MIBG uptake. RESULTS: Twelve (67%) of 18 patients with ventricular tachycardia had regional cardiac sympathetic denervation compared with 1 (8%) of 12 patients who did not have ventricular tachycardia (p = 0.002). In the nine patients with a structurally normal heart and ventricular tachycardia, five (55%) patients had regional cardiac sympathetic denervation compared with zero of nine control patients with a structurally normal heart (p = 0.029). Five patients underwent right ventricular radiofrequency ablation for ventricular tachycardia, and sympathetic denervation was adjacent to the ablation site in one of these patients. CONCLUSIONS: Patients with ventricular tachycardia in the absence of coronary artery disease have abnormal cardiac sympathetic innervation detectable by cardiac sympathetic scintigraphy. The role of regional cardiac sympathetic denervation in arrhythmogenesis remains to be determined.

Prospective study of magnetic resonance imaging and SPECT bone scans in renal allograft recipients: evidence for a self-limited subclinical abnormality of the hip.

We recently reported that typical abnormalities of avascular necrosis (AVN) in magnetic resonance images (MRI) of the hips of asymptomatic renal transplant recipients whose plain radiographs are normal may improve spontaneously and even disappear completely. We present the results of serial bone scans, most of which were performed with single-photon emission computed tomography obtained over periods as long as 24 mo after transplantation in 72 of these patients. Three paired imaging studies (i.e., MR and bone scan performed within 30 days of each other) were available for each of these patients. In three patients, both the MR images and the bone scans showed changes consistent with bilateral AVN within 4 mo after transplantation. All three patients developed hip pain which was bilateral in two and unilateral in one. Two patients (three hips) required surgical intervention at which time AVN was found on pathologic examination of all three hips. None of the remaining 69 patients developed hip pain during the study. However, in nine patients whose MR studies were consistently normal, at least one bone scan was abnormal (13 hips). The presence of AVN was pathologically confirmed in each of the hips subjected to surgery. Where the imaging findings were identical to those in the asymptomatic patients as well as those in whom the imaging abnormality regressed, we suggest that the subclinical imaging abnormalities represent mild AVN, which is reversible in some cases. Since the process was identified in 10 hips by MRI and in 13 hips by bone scan, both studies are needed to detect subclinical AVN. This may be important if treatment of subclinical disease is clearly shown to prevent progression to symptomatic AVN.

Neuronuclear medicine.

The importance of the development of the medical neurosciences is evidenced by the fact that the President of the United States and Congress have declared the 1990s the "decade of the brain." Special emphasis will be placed on managing and treating brain disease and, in particular, salvaging damaged brain from cerebral artery disease, trauma, tumor, and so forth. The advent of brain or cerebral care units in hospitals can be anticipated, analogous to the commonly available coronary care unit that resulted from recent concerted efforts to "conquer" heart disease. This effort will probably lead to a markedly expanded purview for clinical research in central nervous system disease. During the past year, a virtual explosion of publications in the mainstream medical literature on the basic and clinical utilization of nuclear medicine in the neurosciences has occurred. More than 400 substantive papers were published and the majority dealt with some aspect of positron-emission tomography. The more clinically pertinent of these papers are reviewed.

Contrast and nuclear arthrography in loosening of the uncemented hip prosthesis.

The recent popularity of ingrowth or uncemented hip arthroplasties has presented problems in the radiographic diagnosis of loosening because there is no longer a cement interface in which lucencies may be seen. We evaluated a combination of positive contrast and nuclear arthrography to see whether these studies could accurately detect loosening of uncemented femoral components of hip prostheses. We performed routine contrast and nuclear arthrography in 21 patients with ingrowth total hip arthroplasties or bipolar endoprostheses. The results were surgically confirmed in 12 patients. The contrast arthrogram was true positive in 5 and false negative in 5. There were no false positives and 2 true negatives. The nuclear arthrogram was true positive in 7 patients, false negative in 3, and true negative in 2. Taken together, there was only 1 patient in whom both contrast and nuclear arthrography were false negative, and there were no false positives. Thus, when either contrast or nuclear arthrography is positive, the sensitivity of the combined procedures is 90%; when both studies are negative, the specificity is 100%. The combination of contrast and nuclear arthrography is an accurate method of determining loosening of the femoral component of an uncemented hip arthroplasty or bipolar endoprosthesis in the patient with postoperative hip pain.

Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine.

Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a finding is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.

Combined bone scintigraphy and indium-111 leukocyte scans in neuropathic foot disease.

It is difficult to diagnose osteomyelitis in the presence of neurotrophic osteoarthropathy. We performed combined [99mTc]MDP bone scans and indium-111 (111In) leukocyte studies on 35 patients who had radiographic evidence of neuropathic foot disease and clinically suspected osteomyelitis. The [111In]leukocyte study determined if there was an infection and the bone scan provided the anatomic landmarks so that the infection could be localized to the bone or the adjacent soft tissue. Seventeen patients had osteomyelitis and all showed increased [111In]leukocyte activity localized to the bone, giving a sensitivity of 100%. Among the 18 patients without osteomyelitis, eight had no accumulation of [111In]leukocytes, seven had the [111In]leukocyte activity correctly localized to the soft tissue, two had [111In]leukocyte activity mistakenly attributed to the bone, and one had [111In]leukocyte accumulation in a proven neuroma which was mistakenly attributed to bone. These three false-positive results for osteomyelitis reduced the specificity to 83%. Considering only the 27 patients with a positive [111In]leukocyte study, the combined bone scan and [111In]leukocyte study correctly localized the infection to the soft tissues or bone in 89%. Uninfected neurotrophic osteoarthropathy does not accumulate [111In]leukocytes. We found the combined bone scan and [111In] leukocyte study useful for the detection and localization of infection to soft tissue or bone in patients with neuropathic foot disease.

Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application.

Epicardial phenol application or transmural myocardial infarction in dogs produces sympathetic denervation of myocardium apical to the site of the intervention. Because efferent denervation is probably postganglionic, reinnervation most likely occurs but has not been shown. We investigated whether 123I-labeled metaiodobenzylguanidine (MIBG), a norepinephrine analogue taken up by sympathetic nerve terminals, could provide a scintigraphic image that would detect apical sympathetic denervation and possible reinnervation. Dogs underwent MIBG scintigraphic imaging at various times after phenol application or transmural myocardial infarction. The results of MIBG scintigraphy were correlated with electrophysiological responses obtained during ansae subclaviae and norepinephrine stimulation to establish the presence of neural denervation and reinnervation. Apical defects in the MIBG scan, which were associated with either normal perfusion by thallium or a smaller-sized defect, were found consistently in dogs that had apical sympathetic innervation. MIBG scintigraphic images returned to normal after 14 weeks (mean) at a time when reinnervation was shown to have occurred. Thus, the results of MIBG scintigraphy correlated accurately with the presence of denervation and reinnervation established by neuroelectrophysiological testing. Supersensitive refractory period shortening in response to norepinephrine infusion was present after denervation and persisted for more than 3 weeks after scintigraphic and electrophysiological evidence of reinnervation. Conclusions are that 1) MIBG can be used noninvasively to determine the presence of regional myocardial efferent sympathetic denervation and subsequent reinnervation, 2) reinnervation occurs after phenol application or transmural myocardial infarction, and 3) denervation supersensitivity persists even after reinnervation occurs.

In vivo kinetics of canine leukocytes labeled with technetium-99m HM-PAO and indium-111 tropolonate.

Two weeks after the introduction of osteomyelitis in three dogs, autologous leukocytes were dual-labeled with both [99mTc]HM-PAO and [111In]tropolonate, and reinjected. Blood sampling and imaging were then performed. Two weeks later, the same dogs received simultaneous injections of singly-labeled [99mTc]WBC and [111In]WBC for comparison. For both studies, blood samples were drawn over 6 hr to determine the respective blood clearance half-time (TB) and % recovery (%R0) of cell-bound radioactivity. There were no significant differences in the average TB results of the 99mTc and 111In groups, either within or between the dual- and singly-labeled studies. The %R0 of singly-labeled [99mTc]WBC was about half that of the other groups (p less than 0.01); however, this difference was attributed to the dissimilar radiochemical purity of the [99mTc]HM-PAO reagents. Region of interest analysis of the 6 and 24 hr images revealed no significant differences between either cell label in the relative or absolute in vivo uptake at known sites of osteomyelitis, noninfected surgery, and normal bone marrow.

HIPDM-SPECT in patients with medically intractable complex partial seizures. Ictal study.

Both interictal and ictal N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3,propanediamine -single photon emission computed tomography (HIPDM-SPECT) were performed in 16 patients with medically intractable complex partial seizures. Ictal HIPDM-SPECT localized epileptic foci in 13 of 14 patients with unilateral temporal focus and provided confirmative evidence of epileptic focus in 11 patients by demonstrating maximally increased regional cerebral perfusion (rCP) in epileptic foci that had shown decreased rCP in a previous interictal study. Ictal HIPDM-SPECT in two patients with bitemporal foci showed more complicated patterns consisting of slightly increased rCP in bilateral multifocal regions. Ictal HIPDM-SPECT was particularly useful for investigating epileptic foci, and correlation with simultaneously recorded ictal electroencephalograms provided further insight for localizing epileptic foci.

Evaluation of metallic osseous implants with nuclear medicine.

Nuclear medicine has proven to have a valuable role in the evaluation of osseous metallic implants, particularly with joint prostheses, but can assist with evaluation of other appliances as well. The nuclear arthrogram has become an invaluable adjunct to simultaneously performed radiographic contrast arthrography. This application has been best evaluated in what is one of the most common of orthopedic prosthesis problems, namely, loosening of total hip prostheses. Experience indicates that both sensitivity and specificity of loosening of the femoral component can be increased to over 90% through combined use of nuclear with radiographic contrast arthrography. Furthermore the combination of routine skeletal scintimaging with the nuclear arthrogram adds a significant dimension to precise localizing of the nuclear arthrographics agent In-111 chloride. Nuclear medicine also plays an important role in further evaluating the presence of infection associated with metallic implants with In-111 WBC preparations being superior to Ga-67 as the radiopharmaceutical tracer. Infection has been detected with a sensitivity of 73% and a specificity of 93% in our series using combined In-111 WBC and simultaneous skeletal imaging with conventional Tc-99m MDP. Acute infections are more readily identifiable than chronic in association with prostheses.

Comparison of purified indium-111 granulocytes and indium-111 mixed leukocytes for imaging of infections.

Several methods have been proposed for the separation and labeling of white blood cells for the diagnosis of suspected infection. We retrospectively compared 105 patients imaged with 111In purified granulocytes (GRAN) to 106 patients imaged with 111In mixed leukocytes (MIX). We found that in acute infection the sensitivity of GRAN and MIX were both high and not statistically different. In chronic infections the sensitivities were lower than for acute infections. Again, there was no significant difference between GRAN and MIX with the borderline significant exception of MIX being superior to GRAN in chronic soft tissue infections (p = 0.06). We then had independent observers blindly grade the degree of lesion visualization. We found that delayed images visualized the lesions better than early images (p = 0.0001) and acute infection was better visualized than chronic infection (p = 0.03). We concluded that, in routine clinical practice, MIX is probably the agent of choice for three reasons: (a) easier preparation, (b) comparable sensitivity in acute infection and, (c) borderline superior sensitivity in chronic infection.

I-123 HIPDM SPECT imaging and cerebral angiography for EC-IC bypass evaluation.

The use of SPECT in conjunction with I-123 HIPDM is a promising scintigraphic approach to the assessment of regional cerebral tissue perfusion.

HIPDM single photon emission computed tomography brain imaging in partial onset secondarily generalized tonic-clonic seizures.

HIPDM-Single photon emission computed tomography brain imaging was performed during interictal and ictal stages in three patients with complex partial seizures and secondarily generalized tonic-clonic seizures. In all three patients, interictal studies demonstrated decreased regional cerebral perfusion (rCP) and ictal studies showed increased rCP in the epileptogenic region. The demonstration of focal hyperperfusion by SPECT performed during secondarily generalized tonic-clonic seizures suggests that rCP in the epileptic focus remains higher than in other cerebral regions during immediate postictal stages, even in secondarily generalized seizures.