Gebhard Schmid

Contrast Burst Depletion Imaging (CODIM) A New Imaging Procedure and Analysis Method for Semiquantitative Ultrasonic Perfusion Imaging

Background and Purpose— Established methods of ultrasonic perfusion imaging using a bolus application of echo contrast agent provide only qualitative data because of various physical phenomena. This study was intended to investigate whether a new ultrasound perfusion imaging method termed contrast burst depletion imaging (CODIM) may provide semiquantitative measures of parenchymal perfusion independent of examination depth and acoustic energy distribution. Methods— In a system with a constant concentration of contrast agent, analyzing the decrease in image intensity that occurs with microbubble-destructive imaging modes yields parameters that are considered to correlate with tissue perfusion. This method was first evaluated with a perfusion model that showed that the main resulting parameter “perfusion coefficient” (PC) is a monotonic nonlinear function of flow velocity. Seventeen human volunteers were then scanned according to this method with the use of 2 different contrast agents. Results were correlated with those from perfusion-weighted MRI examinations. Results— The PC did not show significant differences in gray matter areas (ranging from 1.466×10−2 s−1 to 1.641×10−2 s−1) of the brain despite different insonation depths (eg, ipsilateral and contralateral thalamus). In contrast, white matter exhibited significantly lower perfusion values in both imaging modes (PC: 0.604×10−2 s−1 to 0.745×10−2 s−1;P <0.05). Conclusions— CODIM is a promising new tool of imaging parenchymal (brain) perfusion in healthy persons. The method provides semiquantitative and depth-independent perfusion parameters and in this way overcomes the limitations of the perfusion methods using a bolus kinetic. Further investigations must be done to evaluate the potential of the method in patients with perfusion deficits.

Dissociation of grey and white matter reduction in spinocerebellar ataxia type 3 and 6: A voxel-based morphometry study

The aim of this study was to examine the different patterns of cerebellar and/or brainstem atrophy in spinocerebellar ataxia (SCA) type 3 and 6. Eighteen patients (SCA3 n=9, SCA6 n=9) and 15 healthy volunteers were studied. Voxel-based morphometry (VBM) was applied to segmented grey matter (GM) and white matter (WM) of high-resolution T1-weighted brain volumes of each group. We found reduction of grey matter in the pons as well as in the vermis in SCA3 as compared to control subjects. In SCA6 significant grey matter loss was found in hemispheric lobules bilaterally as well as in the vermis. White matter analysis revealed significant changes in SCA3, especially in the pons, in the white matter surrounding the dentate nucleus (DN) and in the cerebellar peduncles, whereas no significant white matter reduction was found in SCA6 patients. Our results demonstrate different patterns of grey and white matter affection detected by magnetic resonance imaging (MRI) in SCA3 and SCA6 patients, confirming the pathological concept of cortical cerebellar atrophy in SCA6. In contrast, SCA3 represents a form of ponto-cerebellar atrophy with predominant affection of pontine nuclei and fibre tracts.

Effective Dose of CT- and Fluoroscopy-Guided Perineural/Epidural Injections of the Lumbar Spine: A Comparative Study

The objective of this study was to compare the effective radiation dose of perineural and epidural injections of the lumbar spine under computed tomography (CT) or fluoroscopic guidance with respect to dose-reduced protocols. We assessed the radiation dose with an Alderson Rando phantom at the lumbar segment L4/5 using 29 thermoluminescence dosimeters. Based on our clinical experience, 4–10 CT scans and 1-min fluoroscopy are appropriate. Effective doses were calculated for CT for a routine lumbar spine protocol and for maximum dose reduction; as well as for fluoroscopy in a continuous and a pulsed mode (3–15 pulses/s). Effective doses under CT guidance were 1.51 mSv for 4 scans and 3.53 mSv for 10 scans using a standard protocol and 0.22 mSv and 0.43 mSv for the low-dose protocol. In continuous mode, the effective doses ranged from 0.43 to 1.25 mSv for 1–3 min of fluoroscopy. Using 1 min of pulsed fluoroscopy, the effective dose was less than 0.1 mSv for 3 pulses/s. A consequent low-dose CT protocol reduces the effective dose compared to a standard lumbar spine protocol by more than 85%. The latter dose might be expected when applying about 1 min of continuous fluoroscopy for guidance. A pulsed mode further reduces the effective dose of fluoroscopy by 80–90%.

Comparison Between Echo Contrast Agent-Specific Imaging Modes and Perfusion-Weighted Magnetic Resonance Imaging for the Assessment of Brain Perfusion

Background and Purpose— Contrast burst imaging (CBI) and time variance imaging (TVI) are new ultrasonic imaging modes enabling the visualization of intravenously injected echo contrast agents in brain parenchyma. The aim of this study was to compare the quantitative ultrasonic data with corresponding perfusion-weighted MRI data (p-MRI) with respect to the assessment of brain perfusion. Methods— Twelve individuals with no vascular abnormalities were examined by CBI and TVI after an intravenous bolus injection of 4 g galactose-based microbubble suspension (Levovist) in a concentration of 400 mg/mL. Complementary, a dynamic susceptibility contrast MRI, ie, p-MRI, of each individual was obtained. In both ultrasound (US) methods and p-MRI, time-intensity curves were calculated offline, and absolute time to peak intensities (TPI), peak intensities (PI), and peak width (PW) of US investigations and TPI, relative cerebral blood flow (CBF) and relative cerebral blood volume (CBV) of p-MRI examinations were determined in the following regions of interest (ROIs): lentiform nucleus (LN), white matter (WM), posterior (PT), and anterior thalamus (AT). In addition, the M2 segment of the middle cerebral artery (MCA) was evaluated in the US, and the precentral gyrus (PG) was examined in the p-MRI examinations. In relation to a reference parenchymal ROI (AT), relative TPIs were compared between the US and p-MRI methods and relative PI of US investigations with the ratio of CBF (rCBF) of p-MRI examinations in identical ROIs. Results— Mean TPIs varied from 18.3±5.0 (AT) to 20.1± 5.8 (WM) to 17.2±4.9 (MCA) seconds in CBI examinations and from 19.4±5.3 (AT) to 20.4±4.3 (WM) to 17.3±4.0 (MCA) seconds in TVI examinations. Mean PIs were found to vary from 581.9±342.4 (WM) to 1522.9±574.2 (LN) to 3400.9± 621.7 arbitrary units (MCA) in CBI mode and from 7.5±4.6 (WM) to 17.5±4.9 (LN) to 46.3±7.1 (MCA) arbitrary units in TVI mode. PW ranged from 7.3±4.5 (AT) to 9.1±4.0 (LN) to 24.3±12.8 (MCA) seconds in CBI examinations and from 7.1±3.9 (AT) to 8.7±3.5 (LN) to 26.7±18.2 (MCA) seconds in TVI examinations. Mean TPI was significantly shorter and mean PI and mean PW were significantly higher in the MCA compared with all other ROIs (P <0.05). Mean TPI of the p-MRI examinations ranged from 22.0±6.9 (LN) to 23.0±6.8 (WM) seconds; mean CBF ranged from 0.0093± 0.0041 (LN) to 0.0043±0.0021 (WM). There was no significant difference in rTPI in any ROI between US and p-MRI measurements (P >0.2), whereas relative PIs were significantly higher in areas with lower insonation depth such as the LN compared with rCBF. Conclusions— In contrast to PI, TPI and rTPI in US techniques are robust parameters for the evaluation of cerebral perfusion and may help to differentiate physiological and pathological perfusion in different parenchymal regions of the brain.

Cardiomyopathy in Friedreich's ataxia‐assessment by cardiac MRI

Cardiomyopathy is an important and frequently life limiting manifestation of Friedreichs ataxia (FA), the most prevalent form of autosomal recessive ataxia. Left ventricular mass is used as primary outcome measure in recent intervention studies but systematic analyses of FA cardiomyopathy are sparse. To assess cardiac hypertrophy by cardiac magnetic resonance imaging (MRI) in vivo, we assessed 41 adult patients with genetically confirmed FA and 33 age‐ and sex‐matched healthy controls by cardiac MRI and echocardiogarphy. Septal hypertrophy and left ventricular mass index were determined by two independent raters. MRI revealed hypertrophy of the interventricular septum in 40% and increased left ventricular mass index in 29% of patients. Interobserver variability was less than 5% for both measures. GAA repeat length had only minor influence on interventricular septum thickness. Left ventricular mass index decreased with age. Severity of ataxia did not correlate with cardiac disease. In echocardiography wall diameter was assessable only in 31 of 41 FA patients with 32% of patients presenting septal hypertrophy and 6% increased left ventricular mass index. We conclude that cardiac hypertrophy is present only in a minority of adult FA patients. If despite this limitation intervention studies use left ventricular mass as outcome measure, MRI is recommended as the most accurate assessment of cardiac anatomy in vivo.

CT-guided epidural/perineural injections in painful disorders of the lumbar spine: Short- and extended-term results

Purpose: Evaluation of short- and extended-term results of repeated epidural/perineural injections (EDT/PRT) of corticoids in painful afflictions of the lumbar spine.Methods: Thirty-two patients who had persistent radicular or low back pain for more than 6 weeks were treated with CT-guided injection therapy. By EDT/PRT, 40 mg of triamcinolonacetonid was injected either periradicularly or by a direct intraspinal epidural method at intervals of 3 weeks. Altogether, 140 EDT/PRT were performed in 32 patients (mean 4.4, range 2–8). In nine patients partial facet joint denervation with 1–2 ml of 50% alcohol solution was combined with EDT/PRT to reduce low back pain. Before and after treatment and at follow-up (mean 9.6 months), treatment success was evaluated on a visual analog scale and by physical examination (good=>50% improvement, moderate=20%–50%, no improvement=<20%).Results: Short-term (end of therapy) good or moderate improvement was achieved in 91% of patients, extended-term (mean 9.6 months) in 56%. Regarding certain subgroups, those with disc herniations of the lumbar spine showed a better outcome with good or moderate improvement in 95% short-term and 69% extended-term than those with spinal stenosis who had 72% short-term and 28% long-term.Conclusion: Results indicate that CT-guided EDT/PRT in combination with partial facet joint denervation is a safe and effective outpatient treatment.

Imaging of infected total arthroplasty with Tc-99m-labeled antigranulocyte antibody Fab'fragments.

Objective: The objective of this study was to evaluate the diagnostic accuracy of Tc-99m-labeled antigranulocyte antibody Fab′ fragments in infected total arthroplasty. Materials and Methods: A total of 38 immunoscintigrams were evaluated retrospectively with 15 to 25 mCi Tc-99m-labeled antigranulocyte antibody-Fab′ fragments. The final diagnosis was assessed by articular puncture or intraoperative sampling. Results: In the total hip replacement group the authors found 10 true positives, 7 true negatives, 8 false positives, and 1 false negative; and in the total knee replacement group they found 4 true positives, 8 true negatives, and no false positives or false negatives. They also found a sensitivity of 93%, a specificity of 65%, and a positive predictive accuracy of 63%. There was a negative predictive accuracy of 94%. Conclusion: The high negative predictive accuracy in the whole group suggests that the scan can be used to exclude infection in most cases. Negative results with a high clinical suspicion merits further investigation. A positive result will require further correlative imaging, especially for total knee replacement.

Cross-modal processing in auditory and visual working memory

This study aimed to further explore processing of auditory and visual stimuli in working memory. Smith and Jonides (1997) [Smith, E.E., Jonides, J., 1997. Working memory: A view from neuroimaging. Cogn. Psychol. 33, 5-42] described a modified working memory model in which visual input is automatically transformed into a phonological code. To study this process, auditory and the corresponding visual stimuli were presented in a variant of the 2-back task which involved changes from the auditory to the visual modality and vice versa. Brain activation patterns underlying visual and auditory processing as well as transformation mechanisms were analyzed. Results yielded a significant activation in the left primary auditory cortex associated with transformation of visual into auditory information which reflects the matching and recoding of a stored item and its modality. This finding yields empirical evidence for a transformation of visual input into a phonological code, with the auditory cortex as the neural correlate of the recoding process in working memory.

Therapeutic strategies in Friedreich’s ataxia

Friedreichs ataxia is caused by a pronounced lack of frataxin, a mitochondrial protein of not fully understood function. Lack of frataxin homologues in yeast and mice leads to increased sensitivity to oxidative stress, depletion of proteins with iron-sulfur clusters like respiratory chain complexes I-III and aconitase, and to iron accumulation in mitochondria. Similar effects have been demonstrated in human disease with increased markers of oxidative DNA damage in urine and impaired oxidative phosphorylation in in vivo exercise studies using 31 Phosphorus magnetic resonance spectroscopy (31P-MRS). Therapeutical trials mainly focus on antioxidative treatment with coenzyme Q10 or its short-chain variant idebenone. Promising effects on cardiac hypertrophy in uncontrolled preliminary studies contrast with minor effects in controlled trials and no effect of antioxidants on neurological deficits has been established. Preliminary encouraging 31P-MRS data exist for the treatment with L-carnitine but not with creatine. However, all these interventions may take effect too late in the pathogenic process. Alternative strategies aiming at an enhancement of frataxin by stem cell transplantation, gene transfer or frataxin supplementation are desirable. Additionally, more efficient biomarkers are needed to monitor treatment effects.

Imaging osteomyelitis with Tc-99m-labeled antigranulocyte antibody Fab' fragments.

Purpose The purpose of this study was to evaluate the diagnostic value of Tc-99m-labeled antigranulocyte antibody fragments in the diagnosis of osteomyelitis. Materials and Methods Thirty immunoscintigrams were evaluated retrospectively with 740 MBq (20 mCi) Tc-99m-labeled antigranulocyte antibodies. The final diagnoses were confirmed by histology, magnetic resonance imaging, computed tomography, and clinical follow-up. Results In the retrospective analysis, 20 of 30 patients (67%) demonstrated a true-positive result. Three of 30 patients (10%) had a false-positive result. A false-negative result was found in a diabetic patient with a perforating ulcer of the foot. Six of 30 patients had a true-negative result. A high sensitivity of 95%, a relatively high specificity of 67%, and a high diagnostic accuracy of 86% were present in this study. Conclusion Tc-99m labeled monoclonal antibody–Fab′ fragments are suitable for the detection of osteomyelitis. Its clinical application is simple. Its use guarantees a reliable and accurate diagnostic result just 1 to 2 hours after injection, making a late scan unnecessary. Coxarthrosis or hyperostosis can lead to false-positive results. A perforating ulcer of the foot may result in a false-negative conclusion.