Alex Maes

LONG‐TERM ELECTRICAL CAPSULAR STIMULATION IN PATIENTS WITH OBSESSIVE‐COMPULSIVE DISORDER

OBJECTIVEBecause of the irreversibility of lesioning procedures and their possible side effects, we studied the efficacy of replacing bilateral anterior capsulotomy with chronic electrical capsular stimulation in patients with severe, long-standing, treatment-resistant obsessive-compulsive disorder. METHODSWe stereotactically implanted quadripolar electrodes in both anterior limbs of the internal capsules into six patients with severe obsessive-compulsive disorder. Psychiatrists and psychologists performed a double-blind clinical assessment. A blinded random crossover design was used to assess four of those patients, who underwent continuous stimulation thereafter. RESULTSThe psychiatrist-rated Yale-Brown Obsessive Compulsive Scale score was lower in the stimulation-on condition (mean, 19.8 ± 8.0) than in the postoperative stimulator-off condition (mean, 32.3 ± 3.9), and this stimulation-induced effect was maintained for at least 21 months after surgery. The Clinical Global Severity score decreased from 5 (severe; standard deviation, 0) in the stimulation-off condition to 3.3 (moderate to moderate-severe; standard deviation, 0.96) in the stimulation-on condition. The Clinical Global Improvement scores were unchanged in one patient and much improved in the other three during stimulation. During the stimulation-off period, symptom severity approached baseline levels in the four patients. Bilateral stimulation led to increased signal on functional magnetic resonance imaging studies, especially in the pons. Digital subtraction analysis of preoperative [18F]2-fluoro-2-deoxy-d-glucose positron emission tomographic scans and positron emission tomographic scans obtained after 3 months of stimulation showed decreased frontal metabolism during stimulation. CONCLUSIONThese observations indicate that capsular stimulation reduces core symptoms 21 months after surgery in patients with severe, long-standing, treatment-refractory obsessive-compulsive disorder. The stimulation elicited changes in regional brain activity as measured by functional magnetic resonance imaging and positron emission tomography.

Histological alterations in chronically hypoperfused myocardium. Correlation with PET findings.

BackgroundIn patients with chronic coronary artery disease (CAD) and left ventricular dysfunction, flow/metabolic studies of the myocardium with positron emission tomography (PET) are able to distinguish viable but dysfunctional myocardium from irreversible ischemic injury and scar tissue. In this study, PET findings of blood flow and metabolism in chronically hypoperfused myocardium were correlated with histology. Methods and ResultsWe studied 33 patients suffering from CAD. In each patient, myocardial blood flow and metabolism were measured with PET 1 or 2 days before revascularization. During surgery, transmural biopsies were taken from the left ventricular anterior wall and planimetrically scored for the degree of myolysis (sarcomere loss). The amount of connective tissue was calculated using morphometric techniques. Contrast ventriculography demonstrated abnormal wall motion in 23 patients. Fourteen patients with a mismatch pattern (decreased flow with preserved metabolism) in the biopsy region after quantitative analysis of the PET data showed 11±6 vol% fibrosis and 25±13% cells with sarcomere loss. The space formerly occupied by sarcomeres was mainly replaced by glycogen and mitochondria. A significant wall motion improvement was noted 3 months after surgery. Nine patients showed a match pattern (concordant flow/metabolism defects). The biopsies revealed 35±25% fibrosis and 24±15% glycogen-storing cells. The biopsies of the 10 patients with normal anterior wall motion showed 8±4% fibrosis and 12±8% glycogen-accumulating cells. ConclusionsIt can be concluded that areas with impaired wall motion and a PET match pattern show extensive fibrosis. Regions with reduced flow and preserved FDG metabolism, however, contain predominantly viable cells. In these regions, significant recovery of wall motion is found after revascularization. Regions with normal wall motion contain predominantly viable cells. Cells with reduced contractile material and increased glycogen content are mainly found in areas with wall motion impairment but are also present in areas with normal wall motion and a severe stenosis of the coronary vessel.

Clinical Value of [18F]fluoro-Deoxyglucose Positron Emission Tomography for Patients with Fever of Unknown Origin

We describe the diagnostic contribution of [ 18 F]fluoro-deoxyglucose (FDG) positron emission tomography (PET) scan in 58 consecutive cases of fever of unknown origin (FUO) and compare this new approach with gallium scintigraphy. This investigation was performed from March 1996 through October 1998 at Gasthuisberg University Hospital in Leuven, Belgium. A final diagnosis was established for 38 patients (64%). Forty-six FDG-PET scans (79%) were abnormal; 24 of these abnormal scans (41% of the total number of scans) were considered helpful in diagnosis, and 22 (38% of the total number) were considered noncontributory to the diagnosis. In a subgroup of 40 patients (69%), both FDG-PET and gallium scintigraphy were performed. FDG-PET scan and gallium scintigraphy were normal in 23% and 33% of these cases, respectively; helpful in diagnosis in 35% and 25%, respectively; and noncontributory in 42% each. All foci of abnormal gallium accumulation were also detected by use of an FDG-PET scan. We conclude that FDG-PET is a valuable second-step technique in patients with FUO because it yielded diagnostic information in 41% of the patients in whom the probability of a definite diagnosis was only 64%. FDG-PET scan compares favorably with gallium scintigraphy for this indication. Because of the quick results (within hours instead of days), FDG-PET scan may replace gallium scintigraphy as a radiopharmaceutical for the evaluation of patients with FUO.

Impaired Myocardial Tissue Perfusion Early After Successful Thrombolysis Impact on Myocardial Flow, Metabolism, and Function at Late Follow-up

BACKGROUND Impaired tissue reperfusion after successful recanalization of an epicardial coronary artery has been documented both in animals and in patients with acute myocardial infarction. Whether this phenomenon can be demonstrated with positron emission tomography (PET) and whether it has an effect on late recovery of flow, metabolism, and function are unknown. METHODS AND RESULTS Thirty patients with an acute myocardial infarction and TIMI flow grade 3 of the infarcted vessel at 90 minutes after thrombolytic therapy were studied. Within 24 hours after thrombolysis, at 5 days and at 3 months, myocardial blood flow was measured with 13NH3. 18FDG uptake was measured at 5 days. Radionuclide left ventricular angiograms were acquired at 5 days and at 3 months. In 11 patients (37%), regional myocardial flow was severely impaired (< 50% of normally perfused myocardium) despite successful thrombolysis. No recovery of left ventricular function occurred in any of these patients at 3 months. In 12 patients (40%), intermediate flows (50% to 75% of normal) were found, with functional improvement after angioplasty only in regions with a PET mismatch. Seven patients (23%) had high flow values early after successful thrombolysis (> 75% of normal) and showed preserved regional contractile function at 3 months. CONCLUSIONS This study is the first demonstration with PET of impaired myocardial tissue perfusion in patients with an acute myocardial infarction after successful thrombolysis. Functional recovery of the reperfused myocardium is observed only when adequate tissue flow is restored. PET may be helpful in selecting patients in whom additional revascularization can improve recovery of left ventricular function.

Defining the Transmurality of a Chronic Myocardial Infarction by Ultrasonic Strain-Rate Imaging Implications for Identifying Intramural Viability: An Experimental Study

Background—In a correlative functional/histopathologic study, we investigated the regional deformation characteristics of both chronic nontransmural and transmural infarctions before and after a dobutamine challenge. Methods and Results—After stenosing copper-coated stent implantation to produce circumflex artery endothelial proliferation, 18 pigs were followed up for 5 weeks. Posteuthanasia histology showed 10 to have a nontransmural and 8 a transmural infarction. Eight nonstented animals served as controls. Regional radial function was monitored by measuring ultrasound-derived peak systolic strain rates (SRSYS) and systolic strains (&egr;SYS) (1) before stent implantation and (2) at 5 weeks, at baseline (bs) and during an incremental dobutamine infusion. In controls, dobutamine induced a linear increase in SRSYS (dobutamine: bs, 4.8±0.4 s−1; 20 &mgr;g · kg−1 · min−1, 9.9±0.7 s−1;P <0.0001) and an initial increase of &egr;SYS at low dose (bs, 58±5%; at 5 &mgr;g · kg−1 · min−1, 78±6%;P <0.05) but a subsequent decrease during higher infusion rates. In the nontransmural group, bs SRSYS and &egr;SYS were significantly lower than prestent values (SRSYS, 2.9±0.5 s−1 and &egr;SYS, 32±6%, P <0.05 versus prestent). During dobutamine infusion, SRSYS increased slightly at 5 &mgr;g · kg−1 · min−1 (4.7±0.6 s−1, P <0.05) but fell during higher infusion rates, whereas &egr;SYS showed no change. For nontransmural infarctions, transmural scar extension correlated closely with &egr;SYS at bs (r =0.88). For transmural infarctions, SRSYS at bs was significantly reduced and &egr;SYS was almost not measurable (SRSYS, 1.8±0.3 s−1; &egr;SYS, 3±4%). Both deformation parameters showed no further change during the incremental dobutamine infusion. Conclusions—Ultrasonic deformation values could clearly differentiate chronic nontransmural from transmural myocardial infarction. The transmural extension of the scar could be defined by the regional deformation response.

Only Hibernating Myocardium Invariably Shows Early Recovery After Coronary Revascularization

BACKGROUND The aims of this study were to identify hibernating myocardium (hypocontractile, hypoperfused viable myocardium that regains contractility after revascularization) in the clinical setting and to predict functional outcome in patients with coronary artery disease after coronary revascularization. METHODS AND RESULTS Preoperative data related to the anterior free wall of the left ventricle were collected in 50 coronary bypass surgery candidates (positron emission tomography [PET], [13N]NH3 for flow, and [18F]FDG for metabolism [MET]; equilibrium-gated nuclear angiography [EGNA] for regional ejection fraction [REF]; and histological data from myocardial biopsies for percentage fibrosis and viable myocytes). Three months after surgery, the patients had follow-up PET and EGNA investigations. A principal-components analysis identified four patient clusters. Cluster 1 (n = 9) had normal viable myocardium. Cluster 2 (n = 18) had viable hypocontractile myocardium (REF, 39 +/- 12%) showing a PET mismatch pattern. Cluster 3 (n = 16) had viable hypocontractile myocardium associated with morphological myocyte injury showing a matched moderate decrease in flow (66 +/- 11%) and MET (70 +/- 11%). Cluster 4 (n = 7) had hypocontractile myocardium with mainly scar tissue (fibrosis, 74 +/- 12%). After surgery, only cluster 2, with hibernating myocardium, showed significant improvement in REF (from 39 +/- 12% to 50 +/- 13%, P < .05). Cluster 3, with sites of morphological myocyte injury, showed no recovery. The stepwise logistic regression showed a combination of low preoperative REF and high MET to be the best predictor of functional recovery (P < .008). CONCLUSIONS Multivariate analysis identifies hibernating myocardium showing early postrevascularization recovery, as opposed to viable but myolytic myocardium with no early recovery. Postrevascularization recovery can be predicted (combination of low REF and high MET) by noninvasive techniques.

Assessment of Myocardial Viability in Chronic Coronary Artery Disease Using Technetium-99m Sestamibi SPECT:: Correlation With Histologic and Positron Emission Tomographic Studies and Functional Follow-Up

OBJECTIVES The value of 99mTc-sestamibi (2-methoxy-isobutyl isonitrile [MIBI]) as a viability tracer was investigated in patients undergoing coronary artery bypass graft surgery. BACKGROUND Initial studies claim that rest MIBI single-photon emission computed tomographic (SPECT) studies can be used to assess myocardial viability. METHODS Thirty patients with a severely stenosed left anterior descending coronary artery and wall motion abnormalities were prospectively included. The patients underwent a MIBI rest study, a positron emission tomographic (PET) flow (13NH3) and metabolism (18F-deoxyglucose) study and nuclear angiography before undergoing bypass surgery. A preoperative transmural biopsy specimen was taken from the left ventricular anterior wall. Morphometry was performed to assess percent fibrosis. After 3 months, radionuclide angiography was repeated. RESULTS Statistically significant higher MIBI values were found in the group with myocardial viability as assessed by PET than in the group with PET-assessed nonviability (p < 0.01). Significantly higher MIBI values were found in the group with enhanced contractility at 3 months (76 +/- 13% vs. 53 +/- 22%, p < 0.01). A linear relation was found between MIBI uptake and percent fibrosis in the biopsy specimen (r = 0.78, p < 0.00001). When maximizing the threshold for assessment of viability with MIBI by using functional improvement as the reference standard, a cutoff value of 50% was found, with positive and negative predictive values of 82% and 78%, respectively. CONCLUSIONS 99mTc MIBI uptake was significantly higher in PET-assessed viable areas and in regions with enhanced contractility at 3 months. A linear relation was found between percent fibrosis and MIBI uptake. An optimal threshold of 50% was found for prediction of functional recovery.

Remote Myocardial Dysfunction After Acute Anterior Myocardial Infarction: Impact of Left Ventricular Shape on Regional Function A Magnetic Resonance Myocardial Tagging Study

OBJECTIVES We sought to evaluate regional morphology and function in patients in their first week after having a reperfused anterior myocardial infarction (MI) using magnetic resonance (MR) myocardial tagging. BACKGROUND The mechanism of myocardial dysfunction in the remote, noninfarct-related regions is an unresolved issue to date. METHODS Sixteen patients with a first reperfused transmural anterior MI were studied with MR tagging at 5 +/- 2 days after the event, and the results were compared with those of an age-matched control group regions. The left ventricle (LV) was divided into infarct, adjacent and remote regions. Magnetic resonance tagging provided information on the regional ventricular morphology and function. RESULTS Morphologically, an increase of the circumferential radius of curvature was found in the remote myocardium, whereas the longitudinal radius of curvature was increased in all regions of the LV. A significant increase in apical sphericity was also found. A significant reduction in strain and function was found not only in the infarct region, but also in the adjacent and remote myocardium. The loss in regional ejection fraction in the remote myocardium (61.4 +/- 11.7% in patients vs. 68.7 +/- 10.0% in control subjects, p < 0.0001) was related to a significant reduction of the longitudinal and circumferential strain, whereas systolic wall thickening was preserved. CONCLUSIONS Remote myocardial dysfunction contributes significantly to the loss in global ventricular function. This could be secondary to morphologic changes in the infarct region, leading to an increased systolic longitudinal wall stress without loss of intrinsic contractility in the remote regions.

Unexplained rising carcinoembryonic antigen (CEA) in the postoperative surveillance of colorectal cancer: the utility of positron emission tomography (PET)

The aim of the study was to evaluate the use of positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) in patients with unexplained rising carcinoembryonic antigen (CEA) in the postoperative surveillance of colorectal cancer. 50 consecutive patients with elevated CEA levels and a completely normal (n=31) or equivocal (n=19) conventional diagnostic work-up (CDW) were retrospectively selected. All PET images were reviewed with full knowledge of the CDW. The gold standard consisted of histology, or clinical follow-up of more than 1 year. Recurrent disease was established in 56 lesions in 43 patients. On a patient-based analysis, the sensitivity of FDG-PET was 34/43 (79%), and the positive predictive value 34/38 (89%). In 14/50 patients (28%), the FDG-PET findings led to a surgical resection with curative intent. On a lesion-based analysis, FDG-PET detected 42/56 lesions (sensitivity: 75%), the positive predictive value was 79% (42/53). These results demonstrate that FDG-PET can have a clear impact on patient management in patients with an unexplained elevation in CEA levels.

Whole-body PET with FDG for the diagnosis of recurrent gastric cancer

Abstract. This retrospective study was designed to assess the accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in diagnosing recurrence of gastric cancer. Thirty-three patients who had received surgical treatment for gastric cancer with curative intent and who had subsequently undergone FDG-PET for suspected recurrence were retrieved from the PET database. All patients were reviewed with full knowledge of prior conventional diagnostic work-up. Results were compared with a gold standard, consisting of histological confirmation or radiological and clinical follow-up. The gold standard established disease recurrence in 20/33 patients (prevalence 61%). Sensitivity and specificity of FDG-PET for the diagnosis of recurrence were 70% (14/20) and 69% (9/13), respectively. Positive and negative predictive values were 78% (14/18) and 60% (9/15), respectively. Of the six false-negative cases, all had intra-abdominal lesions (three had generalised abdominal metastases, one liver metastasis, one local recurrence and one ovarian metastasis). In the subgroup with previous signet cell differentiation of the primary tumour (n=13, disease prevalence 62%), sensitivity was 62% (5/8) and specificity, 60% (3/5). Survival analysis for the entire patient group using Kaplan-Meier statistics yielded a longer survival in the PET-negative group (mean±SD, 21.9±19.0 months) than in the PET-positive group (mean±SD, 9.2±8.2 months) (P=0.01). In the patient group with proven recurrence (n=20), the mean survival for the PET-negative group was 18.5 (±12.5) months, as compared with 6.9 (±6.5) months for the PET-positive group (P=0.05). Because of its poor sensitivity and low negative predictive value, FDG-PET is not suited for screening purposes in the follow-up of treated gastric cancer. However, FDG-PET appears to provide important additional information concerning the prognosis of recurrent gastric cancer.