The accuracy and safety aspects of a novel robotic needle guide manipulator to perform transrectal prostate biopsies.

PURPOSE: To introduce a new in-house developed pneumatically controlled magnetic field compatible manipulator as an aid to perform magnetic resonance (MR)-guided biopsies of the prostate. METHODS: A pneumatic controlled manipulator with five degrees of freedom constructed of plastic to achieve magnetic field compatibility was developed to guide biopsies. A risk analysis, mechanical tests, and RF safety tests with respect to needle tip heating were performed to assure future patient safety and to meet standard safety requirements for the use in a medical environment. The accuracy of needle positioning with the needle guide manipulator to sample a predefined target was measured in agar phantoms on a 3 T whole body MR system. The in-plane error was used to evaluate the accuracy, which is defined as the orthogonal distance between target and biopsy needle. The time for each step in the biopsy procedure was recorded to evaluate the procedure time. The influence of the insertion angle with respect to the static field of the MR scanner on the needle artifact was investigated. RESULTS: The risk analyses met patient safety requirements. No RF induced local heating around the needle tip was observed. The average in-plane error in 19 measurements was 3.0 mm (range 0-5.6 mm). The average time needed for manipulation to place the needle guide in the desired position was 5 min (range 3-8 min). Total procedure time was 30 min. The needle artifact size increases with the insertion angle with respect to the static field of the MR scanner. CONCLUSIONS: The new MR compatible manipulator can be used safely for patient care. It showed a high accuracy and short total procedure time, demonstrating great potential to improve the transrectal prostate biopsy procedure.

Detectability of motions in AAA with ECG-gated CTA: a quantitative study.

PURPOSE: ECG-gated CT enables the visualization of motions caused by the beating of the heart. Although ECG gating is frequently used in cardiac CT imaging, this technique is also very promising for evaluating vessel wall motion of the aortic artery and the motions of (stent grafts inside) abdominal aortic aneurysms (AAA). Late stent graft failure is a serious complication in endovascular repair of aortic aneurysms. Better understanding of the motion characteristics of stent grafts will be beneficial for designing future devices. In addition, these data can be valuable in predicting stent graft failure in patients. To be able to reliably quantify the motion, however, it is of importance to know the performance and limitations of ECG gating, especially when the motions are small, as is the case in AAA. Since the details of the reconstruction algorithms are proprietary information on the CT manufacturers and not in the public domain, empirical experiments are required. The goal of this study is to investigate as to what extent the motions in AAA can be measured using ECG-gated CT. The authors quantitatively investigate four aspects of motion in ECG-gated CT: The detectability of the motion of objects at different amplitudes and different periodic motions, the temporal resolution, and the volume gaps that occur as a function of heart rate. METHODS: They designed an experiment on a standard static phantom to empirically determine temporal resolution. To investigate motion amplitude and frequency, as well as patient heart rate, they designed dynamic experiments in which a home-made phantom driven by a motion unit moves in a predetermined pattern. RESULTS: The duration of each ECG-gated phase was found to be 185 ms, which corresponds to half of the rotation time and is thus in accordance with half scan reconstruction applied by the scanner. By using subpixel localization, motions become detectable from amplitudes of as small as 0.4 mm in the x direction and 0.7 mm in the z direction. With the rotation time used in this study, motions up to 2.7 Hz can be reliably detected. The reconstruction algorithm fills volume gaps with noisy data using interpolation, but objects within these gaps remain hidden. CONCLUSIONS: This study gives insight into the possibilities and limitations for measuring small motions using ECG-gated CT. Application of the experimental method is not restricted to the CT scanner of a single manufacturer. From the results, they conclude that ECG-gated CTA is a suitable technique for studying the expected motions of the stent graft and vessel wall in AAA.

Impact of dynamic computed tomographic angiography on endograft sizing for endovascular aneurysm repair.

PURPOSE: To quantify dynamic changes in aortoiliac dimensions using dynamic electrocardiographically (ECG)-gated computed tomographic angiography (CTA) and to investigate any potential impact on preoperative endograft sizing in relation to observer variability. METHODS: Dynamic ECG-gated CTA was performed in 18 patients with abdominal aortic aneurysms. Postprocessing resulted in 11 datasets per patient: 1 static CTA and 10 dynamic CTA series. Vessel diameter, length, and angulation were measured for all phases of the cardiac cycle. The differences between diastolic and systolic aneurysm dimensions were analyzed for significance using paired t tests. To assess intraobserver variability, 20 randomly selected datasets were analyzed twice. Intraobserver repeatability coefficients (RC) were calculated using Bland-Altman analysis. RESULTS: Mean aortic diameter at the proximal neck was 21.4+/-3.0 mm at diastole and 23.2+/-2.9 mm at systole, a mean increase of 1.8+/-0.4 mm (8.5%, p<0.01). The RC for the aortic diameter at the level of the proximal aneurysm neck was 1.9 mm (8.9%). At the distal sealing zones, the mean increase in diameter was 1.7+/-0.3 mm (14.1%, p<0.01) for the right and 1.8+/-0.5 mm (14.2%, p<0.01) for the left common iliac artery (CIA). At both distal sealing zones, the mean increase in CIA diameter exceeded the RC (10.0% for the right CIA and 12.6% for the left CIA). CONCLUSION: The observed changes in aneurysm dimension during the cardiac cycle are small and in the range of intraobserver variability, so dynamic changes in proximal aneurysm neck diameter and aneurysm length likely have little impact on preoperative endograft selection. However, changes in diameter at the distal sealing zones may be relevant to sizing, so distal oversizing of up to 20% should be considered to prevent distal type I endoleak.

Automatic segmentation of the wire frame of stent grafts from CT data.

Endovascular aortic replacement (EVAR) is an established technique, which uses stent grafts to treat aortic aneurysms in patients at risk of aneurysm rupture. Late stent graft failure is a serious complication in endovascular repair of aortic aneurysms. Better understanding of the motion characteristics of stent grafts will be beneficial for designing future devices. In addition, analysis of stent graft movement in individual patients in vivo can be valuable for predicting stent graft failure in these patients. To be able to gather information on stent graft motion in a quick and robust fashion, we propose an automatic method to segment stent grafts from CT data, consisting of three steps: the detection of seed points, finding the connections between these points to produce a graph, and graph processing to obtain the final geometric model in the form of an undirected graph. Using annotated reference data, the method was optimized and its accuracy was evaluated. The experiments were performed using data containing the AneuRx and Zenith stent grafts. The algorithm is robust for noise and small variations in the used parameter values, does not require much memory according to modern standards, and is fast enough to be used in a clinical setting (65 and 30s for the two stent types, respectively). Further, it is shown that the resulting graphs have a 95% (AneuRx) and 92% (Zenith) correspondence with the annotated data. The geometric model produced by the algorithm allows incorporation of high level information and material properties. This enables us to study the in vivo motions and forces that act on the frame of the stent. We believe that such studies will provide new insights into the behavior of the stent graft in vivo, enables the detection and prediction of stent failure in individual patients, and can help in designing better stent grafts in the future.

Spectroscopic imaging of the mouse brain.

Magnetic resonance spectroscopic imaging (MRSI) of the mouse brain reveals a wealth of metabolic information, not only from a single region of interest (single voxel), but spatially mapped over potentially the entire brain. However, MRSI requires challenging methods before the data can be obtained accurately. When applied in vivo, MRSI is generally combined with volume-selective spin perturbation to exclude artifact originating from outside the volume of interest. To obtain good magnetic field (B (0)) uniformity at this volume, accurate B (0) shimming is required. Finally, the immensely large signals originating from water spins need to be suppressed to prevent sidebands that contaminate the spectra, or even saturate the dynamic range of the MR receiver. This chapter describes solutions for these challenges and ends with a rationale between single-voxel MRS versus MRSI.

In vivo magnetic resonance spectroscopy of transgenic mouse models with altered high-energy phosphoryl transfer metabolism.

Studies of transgenic mice provide powerful means to investigate the in vivo biological significance of gene products. Mice with an under- or overexpression of enzymes involved in high-energy phosphoryl transfer (approximately P) are particulary attractive for in vivo MR spectroscopy studies as the substrates of these enzymes are metabolites that are visible in MR spectra. This review provides a brief overview of the strategies used for generation and study of genetically altered mice and introduces the reader to some practical aspects of in vivo MRS studies on mice. The major part of the paper reviews results of in vivo MRS studies on transgenic mice with alterations in the expression of enzymes involved in approximately P metabolism, such as creatine kinase, adenylate kinase and guanidinoacetate methyl transferase. The particular metabolic consequences of these enzyme deficiencies in skeletal muscle, brain, heart and liver are addressed. Additionally, the use of approximately P systems as markers of gene expression by MRS, such as after viral transduction of genes, is described. Finally, a compilation of tissue levels of metabolites in skeletal muscle, heart and brain of wild-type and transgenic mice, as determined by in vivo MRS, is given. During the last decade, transgenic MRS studies have contributed significantly to our understanding of the physiological role of phosphotransfer enzymes, and to the view that these enzymes together build a much larger metabolic energy network that is highly versatile and can dynamically adapt to intrinsic genotoxic and extrinsic physiological challenges.

Phosphorylated guanidinoacetate partly compensates for the lack of phosphocreatine in skeletal muscle of mice lacking guanidinoacetate methyltransferase.

The effects of creatine (Cr) absence in skeletal muscle caused by a deletion of guanidinoacetate methyltransferase (GAMT) were studied in a knockout mouse model by in vivo (31)P magnetic resonance (MR) spectroscopy. (31)P MR spectra of hindleg muscle of GAMT-deficient (GAMT-/-) mice showed no phosphocreatine (PCr) signal and instead showed the signal for phosphorylated guanidinoacetate (PGua), the immediate precursor of Cr, which is not normally present. Tissue pH did not differ between wild-type (WT) and GAMT-/- mice, while relative inorganic phosphate (P(i)) levels were increased in the latter. During ischaemia, PGua was metabolically active in GAMT-/- mice and decreased at a rate comparable to the decrease of PCr in WT mice. However, the recovery rate of PGua in GAMT-/- mice after ischaemia was reduced compared to PCr in WT mice. Saturation transfer measurements revealed no detectable flux from PGua to gamma-ATP, indicating severely reduced enzyme kinetics. Supplementation of Cr resulted in a rapid increase in PCr signal intensity until only this resonance was visible, along with a reduction in relative P(i) values. However, the PGua recovery rate after ischaemia did not change. Our results show that despite the absence of Cr, GAMT-/- mice can cope with mild ischaemic stress by using PGua for high energy phosphoryl transfer. The reduced affinity of creatine kinase (CK) for (P)Gua only becomes apparent during recovery from ischaemia. It is argued that absence of Cr causes the higher relative P(i) concentration also observed in animals lacking muscle CK, indicating an important role of the CK system in P(i) homeostasis.

Magnetization transfer effect on the creatine methyl resonance studied by CW off-resonance irradiation in human skeletal muscle on a clinical MR system.

Magnetization transfer (MT) between the mobile (MR-visible) spin pool and immobile (MR-invisible) spin pool of creatine (Cr) was studied on a clinical 1.5 T MR scanner in human skeletal muscle using continuous wave (CW) pre-irradiation as the saturation method for the immobile pool. For this purpose, only slight modifications to the MR system were made. A specially designed electronic circuit was used to couple a CW amplifier to the RF channel of the scanner. The CW pulse power (gammaB(2)/2pi) and pulse length were determined to be approximately 550 Hz and 3 s, respectively, for optimal signal attenuation of the Cr methyl signal. The bound Cr fraction in human gastrocnemius muscle was determined to be 0.4-1.3% using a two-pool exchange model function to describe the MT effect.

MR spectroscopy of muscle and brain in guanidinoacetate methyltransferase (GAMT)-deficient mice: validation of an animal model to study creatine deficiency.

As a model for guanidinoacetate methyltransferase (GAMT) deficiency in humans, a gene knockout mouse model was generated. Here we report on several metabolic abnormalities in these mice, observed by in vivo and in vitro MR spectroscopy. In (1)H MR spectra of brain and hindleg muscle a clearly reduced signal of creatine (Cr) was observed in GAMT-deficient (GAMT-/-) animals. Analysis of the (1)H MR spectra of GAMT-/- brain indicated little or no increase of a signal for guanidinoacetate (Gua). In proton MR spectra of muscle, a broad signal of low intensity was observed for Gua. However, substantial Gua accumulation in intact muscle tissue was unequivocally confirmed in high-resolution magic angle spinning spectra, in which the Gua signal was resolved as one clear sharp singlet. In (31)P MR analysis of brain and hindleg muscle a strongly reduced phosphocreatine (PCr) content was shown. In addition, a signal of phosphorylated Gua at 0.5 ppm upfield of PCr was observed, with much higher intensity in muscle than in brain. This signal decreased when ischemia was applied to the muscle and recovered after ischemia was released. Overall, the in vivo (31)P and (1)H MR spectroscopy of GAMT-/- mice is similar to that of human GAMT deficiency. This opens up new avenues for the fundamental study of tissue-type dependence of creatine synthesis and transport and for diagnostic and therapeutic aspects of creatine deficiencies in humans.

Severely altered guanidino compound levels, disturbed body weight homeostasis and impaired fertility in a mouse model of guanidinoacetate N-methyltransferase (GAMT) deficiency.

We generated a knockout mouse model for guanidinoacetate N-methyltransferase (GAMT) deficiency (MIM 601240), the first discovered human creatine deficiency syndrome, by gene targeting in embryonic stem cells. Disruption of the open reading frame of the murine GAMT gene in the first exon resulted in the elimination of 210 of the 237 amino acids present in mGAMT. The creation of an mGAMT null allele was verified at the genetic, RNA and protein levels. GAMT knockout mice have markedly increased guanidinoacetate (GAA) and reduced creatine and creatinine levels in brain, serum and urine, which are key findings in human GAMT patients. In vivo (31)P magnetic resonance spectroscopy showed high levels of PGAA and reduced levels of creatine phosphate in heart, skeletal muscle and brain. These biochemical alterations were comparable to those found in human GAMT patients and can be attributed to the very similar GAMT expression patterns found by us in human and mouse tissues. We provide evidence that GAMT deficiency in mice causes biochemical adaptations in brain and skeletal muscle. It is associated with increased neonatal mortality, muscular hypotonia, decreased male fertility and a non-leptin-mediated life-long reduction in body weight due to reduced body fat mass. Therefore, GAMT knockout mice are a valuable creatine deficiency model for studying the effects of high-energy phosphate depletion in brain, heart, skeletal muscle and other organs.