Zsolt Lengyel

A Review on Radiogenic Lhermitte's Sign *

Radiation myelopathy is a rare, but extremely serious side-effect of radiotherapy. Recovery from radiation-induced motor sequelae is rare, whereas, the regeneration of sensory losses is relatively frequent. Among the sensory radiogenic injuries of the spinal cord, Lhermitte’s sign (LS) is most frequent. This review describes the clinical picture and diagnostic imaging signs of radiogenic LS. There have been only a few studies on large patient groups with radiogenic LS, demonstrating a rate of occurrence of 3.6–13%, relating mainly to mantle irradiation or the radiotherapy of head and neck tumors. These cases typically manifest themselves 3 months following radiotherapy and gradually disappear within 6 months. Only 3 LS cases have been described in the English literature with extraordinarily severe symptoms lasting for more than 1 year. MRI, a sensitive tool in the detection of demyelination, failed to reveal any pathological sign accompanying radiogenic LS. However, positron emission tomography demonstrated increased [18F]fluorodeoxyglucose accumulation and [15O]butanol perfusion, but a negligible [11C]methionine uptake in the irradiated spinal cord segments in patients with long-standing LS. These imaging data are suggestive of a close direct relationship between the regional perfusion and metabolism of the spinal cord, very much like the situation in the brain. We postulate that an altered, energy-demanding conduction along the demyelinated axons of patients with chronic radiogenic LS may explain the increased metabolism and perfusion.

Angiography effectively supports the diagnosis of hepatic metastases in medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) belongs in the group of neuroendocrine tumors with early lymphatic and hepatic dissemination. A high rate of undetectable metastases is hypothesized to be responsible for the frequent mismatch between the apparent relatively small tumor burden and the elevated plasma tumor marker level.

Feasibility of 11C-Acetate PET/CT for Imaging of Fatty Acid Synthesis in the Atherosclerotic Vessel Wall

Fatty acids are a common constituent of atherosclerotic plaque and may be synthesized in the plaque itself. Fatty acid synthesis requires acetyl-coenzyme-A (CoA) as a main substrate, which is produced from acetate. Currently, 11C-acetate PET/CT is used for the evaluation of malignancies. There are no data concerning its potential for the characterization of atherosclerotic plaque. Therefore, the purpose of the present study was to examine the prevalence, distribution, and topographic relationship of arterial 11C-acetate uptake and vascular calcification in major arteries. Methods: Thirty-six patients were examined by whole-body 11C-acetate PET/CT. Tracer uptake in various arterial segments was analyzed both qualitatively and semiquantitatively by measuring the blood-pool–corrected standardized uptake value (target-to-background ratio). CT images were used to measure calcified plaque burden. Results: 11C-acetate uptake was observed at 220 sites in 32 (88.8%) of the 36 study patients, and mean target-to-background ratio was 2.5 ± 1.0. Calcified atherosclerotic lesions were observed at 483 sites in 30 (83.3%) patients. Sixty-four (29.1%) of the 220 lesions with marked 11C-acetate uptake were colocalized with arterial calcification. However, only 13.3% of all arterial calcification sites demonstrated increased radiotracer accumulation. Conclusion: Our data indicate the feasibility of using 11C-acetate PET/CT for imaging of fatty acid synthesis in the atherosclerotic vessel wall. This study provides a rationale to incorporating 11C-acetate PET into further preclinical and clinical studies to obtain new insights into fatty acid synthesis in atherosclerotic lesions and to evaluate whether it may be used to monitor pharmacologic intervention with fatty acid synthase inhibitors.

PET identifies transitional metabolic change in the spinal cord following a subthreshold dose of irradiation.

Positron emission tomographic (PET) investigations were performed to obtainin vivo information on symptomless radiation-induced pathological changes in the human spinal cord. PET investigations were carried out prior to radiotherapy and during the regular follow-up in an early hypopharyngeal cancer patient (the spinal cord was irradiated with a biologically effective dose of 80 Gy2), with [18F]fluorodeoxyglucose (FDG), [11C]methionine and [15O]butanol as tracers; radiosensitivity and electroneuronographic (ENG) studies were also performed. A very low background FDG accumulation (mean standardized uptake values, i.e. SUV: 0.84) was observed in the spinal cord before the initiation of radiotherapy. An increased FDG uptake was measured 2 months after the completion of radiotherapy (mean SUV: 1.69), followed by a fall-off, as measured 7 months later (mean SUV: 1.21). By 44 months after completion of irradiation, the FDG accumulation in the irradiated segments of the spinal cord had decreased to a level very close to the initial value (mean SUV: 1.11). The simultaneous [15O]butanol uptake results demonstrated a set of perfusion changes similar to those observed in connection with the FDG accumulation. The patient exhibited an extremely low [11C]methionine uptake within the irradiated and the nonirradiated spinal cord during the clinical course. She has not had any neurological symptoms, and the results of central ENG measurements before radiotherapy and 2 months following its completion proved normal. Radiobiological investigations did not reveal unequivocal signs of an increased radiosensitivity. A transitory increased spinal cord FDG uptake following radiotherapy may be related to the posttherapeutic mild inflammatory and regenerative processes. The normal [11C]methionine accumulation observed is strong evidence against intensive cell proliferation. The high degree of normalization of the temporarily increased FDG uptake of the irradiated spinal cord segments by 44 months is in good agreement with the results of monkey studies, which demonstrated a nearly complete recovery from radiation-induced spinal cord injury.

Right prefrontal activation produced by arterial baroreceptor stimulation: a PET study.

This study was performed to test the hypothesis of greater right hemispheric involvement in the processing of baroreceptor stimuli. Carotid sinus baroreceptors were stimulated by rhythmically decreasing air pressure in a neck chamber, and under control conditions the thorax was stimulated in a similar manner. Changes in regional cerebral blood flow (rCBF) were measured by PET. Baroreceptor stimulation resulted in rCBF increase in the right anterior–inferior prefrontal cortex (Brodmann areas (BA) 10/44/47) and bilaterally in BA 6/8. We conclude that in at least some stages of baroreceptor information processing the right hemisphere plays a greater role than the left hemisphere.

Increased Metabolic Activity in the Spinal Cord of Patients with Long-Standing Lhermitte’s Sign

Purpose:To investigate the pathophysiology of the radiation-induced, chronic Lhermitte’s sign (LS) on the basis of long-standing case histories with partial functional recovery.Patients and Methods:As radiotherapy in two nasopharyngeal cancer patients, a biologically effective dose (BED) of 103.8 Gy2 (case 1) and 94.8 Gy2 (case 2) was delivered to the cervical spinal cord. Neurologic signs relating to the irradiated spinal cord segments developed after 2 months (case 1) and 5 years (case 2), with radiation-induced damage equivalent to grade 3 (case 1) and grade 2 (case 2) toxicity (Common Toxicity Criteria, Version 2.0). The clinical status improved to grade 2 (case 1) and grade 1 (case 2). Positron emission tomography (PET) and fibroblast clonogen assay were applied 25 and 7 years postirradiation, respectively, to characterize this rare clinical picture.Results:PET demonstrated increased [18F]fluorodeoxyglucose (FDG) accumulation and [15O]butanol perfusion, but negligible [11C]methionine uptake in the irradiated spinal cord segments in both patients. In clonogenic assays, fibroblasts from case 1 displayed much higher radiation sensitivity than in healthy controls, while in case 2 the fibroblasts sensitivity was normal.Conclusions:These data suggests a close direct relationship between regional perfusion and metabolism of the spinal cord, similarly as in the brain. The postirradiation recovery may be related to energy-demanding conduction, explaining the increased metabolism and perfusion. The increased radiosensitivity and higher spinal cord BED may have contributed to the more severe sequelae in case 1.Ziel:Untersuchung der Pathophysiologie des strahleninduzierten chronischen Lhermitte-Zeichens auf der Basis der Langzeitbeobachtung von zwei Patienten mit partieller funktioneller Erholung.Patienten und Methodik:Bei zwei Patienten mit Nasopharynxkarzinom wurde die Halswirbelsäule mit einer biologisch effektiven Dosis (BED) von 103,8 Gy2 (Patient 1) bzw. 94,8 Gy2 (Patient 2) bestrahlt. Neurologische Symptome, die auf die bestrahlten Segmente des Zervikalmarks zurückzuführen waren, traten nach 2 Monaten (Patient 1) bzw. nach 5 Jahren (Patient 2) auf, wobei die strahleninduzierte Schädigung einer Grad-3- (Patient 1) bzw. Grad-2-Toxizität (Patient 2) entsprach (Common Toxicity Criteria, Version 2.0). Der klinische Status ging auf Grad 2 (Patient 1) bzw. Grad 1 (Patient 2) zurück. Positronenemissionstomographie (PET) und der Fibroblastenklonogenitätsassay wurden 25 bzw. 7 Jahre nach der Strahlentherapie eingesetzt, um dieses seltene Krankheitsbild zu charakterisieren.Ergebnisse:Im PET zeigten sich bei beiden Patienten eine erhöhte [18F-]Fluorodesoxyglucose-(FDG-)Aufnahme und [15O-] Butanol-Perfusion, jedoch eine vernachlässigbar geringe [11C-]Methionin-Aufnahme in den bestrahlten Segmenten. In den Klonogenitätsassays hatten die Fibroblasten des Patienten 1 eine höhere Strahlungsempfindlichkeit als bei gesunden Kontrollen, während die Fibroblastensensitivität bei Patient 2 normal war.Schlussfolgerungen:Diese Befunde sprechen für eine—ähnlich wie im Gehirn—enge direkte Beziehung zwischen regionaler Perfusion und Metabolismus des Rückenmarks. Die Erholung nach der Strahlentherapie dürfte mit Energie verbrauchenden Prozessen einhergehen, was die Steigerung von Metabolismus und Perfusion erklärt. Die erhöhte Strahlenempfindlichkeit und die höhere BED am Rückenmark können zu den gravierenderen Folgeerscheinungen bei Patient 1 beigetragen haben.

Autopsy verifies demyelination and lack of vascular damage in partially reversible radiation myelopathy

Study design: Case report of recovering radiation myelopathy.Objective: To present autopsy and functional imaging findings on a unique case of slowly recovering radiation myelopathy with the aim of the clarification of the underlying mechanism.Patient: The cervical spinal cord and the distal part of the medulla oblongata of a 36-year-old thyroid cancer patient had been incorrectly irradiated with a total dose of 61 Gy and a fraction size of 3.4 Gy (J Neurol Sci 1999; 163:39–43), resulting in incomplete cervical transection with a 5-month latency period following the termination of radiotherapy. This was followed by a 9.5-year spontaneous improvement until her demise, during which the check-ups were supplemented by positron emission tomography (PET) investigations; these indicated increased [18F]deoxyglucose and [15O]butanol uptakes, but a diminished [11C]methionine accumulation by the irradiated spinal cord segment.Results: Autopsy revealed demyelination (with axonal loss) and neuronal damage in the cervical spinal cord and the distal part of the medulla oblongata. In the same region, only minimal vascular injury (thickening of some of the capillary walls) was detected, but not cell proliferation or chronic inflammation. Bilateral, secondary pyramidal tract degeneration caudal to the irradiated segment was observed. The PET and autopsy findings, although separated by 2 years, are consistent.Conclusions: The pathological state of the spinal cord revealed by the autopsy is concordant with the incomplete cervical transection, implying that the functional recovery is supported by a process that probably differs from the restoration of the mechanism destroyed by the radiotherapy. For the restoration of the function, we suggest an altered conduction mechanism of the action potential, involving an increased number of sodium channels along the demyelinated segments of the injured axons, which is fully congruent with the PET findings.

Correlation of the value of 18F-FDG uptake, described by SUVmax, SUVavg, metabolic tumour volume and total lesion glycolysis, to clinicopathological prognostic factors and biological subtypes in breast cancer.

ObjectiveThe aim of this study was to observe the relationships between different metabolic parameters and clinicopathological features (CPFs) or immunohistochemically defined biological subtypes (IHC-BS) in breast cancer. Materials and methodsEighty-two women (83 lesions, tumour size >15 mm) underwent PET/computed tomography imaging after a core biopsy. Maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) in the primary tumour were calculated and compared with CPFs and IHC-BS. Tumours with oestrogen receptor (ER) positivity were separately investigated in relation to their progesterone receptor (PR) status. ResultsSignificant correlation was found between all metabolic parameters and high nuclear grade or ER status or IHC-BS. All parameters were higher in PR(−) and triple-negative cases than in PR(+) and non-triple-negative tumours, and the correlation was significant for most of the metabolic parameters (except for SUVavg in the case of PR status and MTV in the case of triple negativity). Significant correlation was found only for SUVmax regarding the human epidermal growth factor receptor 2 (HER2) status. There was moderate correlation between the Ki67 expression and the SUVmax or SUVavg. All metabolic parameters were higher in ER(+)/PR(−)/HER2(−) lesions compared with ER(+)/PR(+)/HER2(−) cancers. However, ER(+)/PR(−)/HER2(+) tumours had lower SUVmax and SUVavg compared with ER(+)/PR(+)/HER2(+) lesions. ConclusionOur study confirms that the fluorine-18 fluorodeoxyglucose uptake in primary tumour is associated with distinct CPFs or IHC-BS in breast cancer. SUVmax may reflect tumour metabolism more reliably compared with SUVavg, MTV or total lesion glycolysis. Our preliminary results suggest different biological properties in ER(+) tumours with different PR statuses.

Mediastinal Bulky Tumour in Hodgkin’s Disease and Prognostic Value of Positron Emission Tomography in the Evaluation of Post-Treatment Residual Masses

Among the 193 patients (82 female, 111 male) treated primarily for Hodgkin’s disease at our clinic between 1990 and 2001 and followed up until 2003, 42 (22%) had mediastinal bulky tumours (MBTs) by the Cotswolds criteria. The rate of MBT diagnosis was significantly greater in the early stage of the disease, these patients were younger and – in contrast to the other group – they all received combined therapy. No significant differences were found in the overall and relapse-free survival rate in the two groups, but relapse and death rates were lower in the patients with bulky tumours. Of the total number of patients, 27 underwent a total of 31 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) examinations, mainly for the evaluation of post-treatment residual mass viability. In the 12 positive cases, the majority of patients received further therapy. During the mean follow-up time of 58 months (range 5–98 months) after obtaining negative results, progression of the disease was found in 2 cases 14 and 23 months later, respectively. Based on our results, we conclude that FDG-PET examinations show a good correlation with clinical follow-up results.

Preparation and primary evaluation of [11C]CSC as a possible tracer for mapping adenosine A2A receptors by PET

A 11C labeled selective adenosine A2A antagonist, (E)-8-(3-chlorostyryl)-1,3-dimethyl-7-[11C]methylxanthine [11C]CSC) was prepared by the reaction of (E)-8-(3-chlorostyryl)-1,3-dimethylxanthine and [11C]methyl iodide. The decay-corrected radiochemical yield was 32.3% with a radiochemical purity of 99%, a specific activity of 1.85-5.55 GBq/mumol and a preparation time of 1 h. A primary evaluation of [11C]CSC as a potential tracer for mapping adenosine A2A receptors by positron emission tomography (PET) is also presented. Biodistribution and autoradiographic studies were carried out on Swiss mice and domestic rabbits. In mice the lung showed the highest uptake at 10 min after i.v. injection, followed by the liver, kidney, heart and brain. Inside the brain a high level of radioactivity accumulated in the striatum, in accordance with previous findings on the specific spatial distribution of A2A adenosine receptors and also in the medulla oblongata. Dynamic PET studies on rabbits showed a fast brain uptake of CSC, reaching a maximum in less then 2 min. On the basis of competition experiments with the unlabeled ligand [11C]CSC proves to bind specifically to the appropriate receptor.