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Modern fluoroscopes used for image guidance have become quite complex. Adding to this complexity are the many regulatory and accreditation requirements that must be fulfilled during acceptance testing of a new unit. Further, some of these acceptance tests have pass/fail criteria, whereas others do not, making acceptance testing a subjective and time-consuming task. The AAPM Task Group 272 Report spells out the details of tests that are required and gives visibility to some of the tests that while not yet required are recommended as good practice. The organization of the report begins with the most complicated fluoroscopes used in interventional radiology or cardiology and continues with general fluoroscopy and mobile C-arms. Finally, the appendices of the report provide useful information, an example report form and topics that needed their own section due to the level of detail.

In this article, we review automatic brightness control (ABC) for fluoroscopy imaging systems. Starting from the simple manual control, the discussion is extended to the kV-primary ABC system, and then to the most recent contrast-to-noise ratio optimized (CNR Optimized) automatic dose rate control system (ADRC). The nature of this review article is trifold. First, it describes the ABC/ADRC and associated circuits governing the operation of the fluoroscopy imaging chain. Second, we show the characteristics of a control logic from a radiation physics point of view. Third, we introduce the most recent activities in the evaluation of CNR-optimized fluoroscopy systems and the phantom design that would be compatible with the design concept of the ADRC. Because of these three subject items in the discussion process, this article is also educational in nature written for medical physicists and radiological technologists who might be less familiar with the design concept of fluoroscopy operation, specifically on the ABC and ADRC. We insert a few related matters associated with fluoroscopy automatic control circuits where they seem applicable and appropriate to enhance the understanding of fluoroscopy operation logic.

A common approach to quantify gadolinium (Gd) contrast agents involves measuring the post-contrast change in T1 rate and then using the constant T1 relaxivity R to determine the contrast agent concentration. Because this method is fast and non-invasive, it could be potentially valuable in many areas of brain research. However, to accurately measure contrast agent concentrations in the brain, the T1 relaxivity R of the specific agent must be accurately known. Furthermore, the macromolecular content and compartmentalization of the brain extracellular space (ECS) are expected to significantly alter R from values measured in aqueous solutions. In this study, the T1 relaxivity R of gadolinium-diethylene-triamine penta-acetic acid (Gd-DTPA) was measured following direct interstitial infusions of three different contrast agent concentrations to the parenchyma of rat brains. Changes in magnetic resonance (MR) T1 values were compared to brain slice concentrations determined with inductively coupled plasma atomic emission spectroscopy (ICP-AES) to determine R in 15 rats. Additionally, samples of cerebrospinal fluid, blood and urine were analyzed to evaluate possible Gd-DTPA clearance from the brain. The T1 relaxivity R of Gd-DTPA in the brain ECS was measured to be 5.35 (mM s)(-1) in a 2.4 T field. This value is considerably higher than estimations used in studies by other groups. Measurements of brain Gd-DTPA tissue concentrations using MRI and ICP-AES demonstrated a high degree of coincidence. Clearance of Gd-DTPA was minimal at the time point immediately after infusion. These results suggest that the environment of the brain does in fact significantly affect Gd T1 relaxivity, and that MRI can accurately measure contrast agent concentrations when this relaxivity is well characterized.

The water soluble poly(ethylene glycol) (PEG) functionalized and hydroxylated endohedral trimetallic nitride metallofullerene derivatives, Gd3N@C80[DiPEG(OH)x], have been synthesized and characterized. The 1H MRI relaxivities in aqueous solution were measured for the derivatives with four different molecular weights of PEG (350–5000 Da) at 0.35 T, 2.4 T and 9.4 T. The 350/750 Da PEGs derivatives were found to have the highest relaxivities values among the derivatives, 237/232 mM−1s−1 for r1 and 460/398 mM−1s−1 for r2 (79/77 mM−1s−1 and 153/133 mM−1s−1 based on Gd3+ ion) respectively, at a clinical-range magnetic field of 2.4 T. These represent some of the highest relaxivities reported in the literatures for any commercial or investigational MRI contrast agent. Dynamic light scattering results confirm a larger size distribution for 350/750 Da PEGs derivatives (95/96 nm) relative to longer chain length derivatives, 5000 Da PEG derivatives (37nm). Direct infusion of the optimized 350 Da PEG derivatives into live tumor-bearing rat brains demonstrated an initial uniform distribution and hence, the potential for effective brachytherapy applications when the encapsulated Gd3+ ions are replaced with radioactive 177Lu.

A new magnetic resonance imaging (MRI) contrast agent based on the trimetallic nitride templated (TNT) metallofullerene Gd(3)N@C(80) was synthesized by a facile method in high yield. The observed longitudinal and transverse relaxivities r(1) and r(2) for water hydrogens in the presence of the water-soluble gadofullerene 2 Gd(3)N@C(80)(OH)(approximately 26)(CH(2)CH(2)COOM)(approximately 16) (M = Na or H) are 207 and 282 mM(-1) s(-1) (per C(80) cage) at 2.4 T, respectively; these values are 50 times larger than those of Gd(3+) poly(aminocarboxylate) complexes, such as commercial Omniscan and Magnevist. This high (1)H relaxivity for this new hydroxylated and carboxylated gadofullerene derivative provides high signal enhancement at significantly lower Gd concentration as demonstrated by in vitro and in vivo MRI studies. Dynamic light scattering data reveal a unimodal size distribution with an average hydrodynamic radius of ca. 78 nm in pure water (pH = 7), which is significantly different from other hydroxylated or carboxylated fullerene and metallofullerene derivatives reported to date. Agarose gel infusion results indicate that the gadofullerene 2 displayed diffusion properties different from those of commercial Omniscan and those of PEG5000 modified Gd(3)N@C(80). The reactive carboxyl functionality present on this highly efficient contrast agent may also serve as a precursor for biomarker tissue-targeting purposes.

Targeting tumor vasculature by colchicine site microtubule inhibitors is a new approach in cancer therapy. Here we investigate cis-3, 4′, 5-trimethoxy-3′-aminostilbene (stilbene 5c) in its effect on tumor vascular perfusion, pharmacokinetics, toxicity and therapeutic efficacy in a mouse xenograft model. Tumor xenograft model was established with subcutaneous injection of UCI-101 ovarian cancer cells into nude mice. Tumor blood perfusion was investigated by dynamic contrast-enhanced (DCE) MRI studies. Pharmacokinetic studies were performed by LC/MS/MS to quantify the concentrations of stilbene 5c in plasma. Tumor size was measured by the long and short axes of tumor to calculate tumor volume. Mouse cardiac function study was determined by Doppler echocardiography using the Vevo770TM imaging system. Microvascular density was determined by CD34 staining of tissue sections. Stilbene 5c selectively suppresses tumor perfusion without damaging normal organ perfusion in DCE-MRI studies. Histological sections of normal organs treated with stilbene 5c do not reveal any major toxicity in H&E staining. Microvascular density determined by CD34 staining is unchanged in normal organs, but significantly decreased in tumor after stilbene 5c treatment. Biodistribution study shows that stilbene 5c is not detectable in heart and lung, rapidly decreased in brain, liver, and kidney, but remains high in tumor for more than 3 h after IV injection of stilbene 5c, suggesting preferential accumulation in tumor. Mice treated with 5 days of stilbene 5c had negligible cardiac toxicity based on their normal left ventricular ejection fraction. In vivo efficacy study of stilbene 5c showed that it only suppresses tumor growth by 40% if used alone, but combination with bevacizumab is significantly better. Stilbene 5c is a useful vascular disrupting agent and combination with bevacizumab could be a promising therapy for cancer.

A new magnetic resonance imaging contrast agent containing organophosphonate functional groups was synthesized in high yield by a simple synthesis procedure. This molecule exhibits much higher longitudinal water proton relaxivity (37.0 mM−1 s−1) than commercial Omniscan (Gd-DTPA BMA, 5.7 mM−1 s−1) at 0.35 T. Notably, the relaxivity is larger than that of carboxylated Gd@C82 (16.0 mM−1 s−1) under the same conditions, indicating that the functional groups have an important role on the image contrast enhancement. In addition, the introduction of phosphonate substituents may provide bone-targeting MRI contrast agents.

Astrocyte elevated gene-1 (AEG-1), also known as MTDH (metadherin) or LYRIC, is an established oncogene. However, the physiological function of AEG-1 is not known. To address this question, we generated an AEG-1 knock-out mouse (AEG-1KO) and characterized it. Although AEG-1KO mice were viable and fertile, they were significantly leaner with prominently less body fat and lived significantly longer compared with wild type (WT). When fed a high fat and cholesterol diet (HFD), WT mice rapidly gained weight, whereas AEG-1KO mice did not gain weight at all. This phenotype of AEG-1KO mice is due to decreased fat absorption from the intestines, not because of decreased fat synthesis or increased fat consumption. AEG-1 interacts with retinoid X receptor (RXR) and inhibits RXR function. In enterocytes of AEG-1KO mice, we observed increased activity of RXR heterodimer partners, liver X receptor and peroxisome proliferator-activated receptor-α, key inhibitors of intestinal fat absorption. Inhibition of fat absorption in AEG-1KO mice was further augmented when fed an HFD providing ligands to liver X receptor and peroxisome proliferator-activated receptor-α. Our studies reveal a novel role of AEG-1 in regulating nuclear receptors controlling lipid metabolism. AEG-1 may significantly modulate the effects of HFD and thereby function as a unique determinant of obesity.

This study utilized magnetic resonance imaging (MRI) to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP)-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K) pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary bladder was also markedly reduced. Treatment of the cystitis animals with a specific PI3K inhibitor LY294002 reduced cystitis-induced bladder wall thickening and enlarged the intravesical volumes. To confirm the MRI results, we performed H&E stain postmortem and examined the levels of type I collagen by real-time PCR and western blot. Inhibition of the PI3K in vivo reduced the levels of type I collagen mRNA and protein in the urinary bladder ultimately attenuating cystitis-induced bladder hypertrophy. The bladder mass calculated according to MRI data was consistent to the bladder weight measured ex vivo under each drug treatment. MRI results also showed that the urinary bladder from animals with cystitis demonstrated high magnetic signal intensity indicating considerable inflammation of the urinary bladder when compared to normal animals. This was confirmed by examination of the pro-inflammatory factors showing that interleukin (IL)-1α, IL-6 and tumor necrosis factor (TNF)α levels in the urinary bladder were increased with cystitis. Our results suggest that MRI can be a useful technique in tracing bladder anatomy and examining bladder hypertrophy in vivo during disease development and the PI3K pathway has a critical role in regulating bladder hypertrophy during cystitis.

Object. The goal of this study was to validate a simple, inexpensive, and robust model system to be used as an in vitro surrogate for in vivo brain tissues in preclinical and exploratory studies of infusion-based intraparenchymal drug and cell delivery. Methods. Agarose gels of varying concentrations and porcine brain were tested to determine the infusion characteristics of several different catheters at flow rates of 0.5 and 1 µl per minute by using bromophenol blue (BPB) dye (molecular weight [MW] ∼690) and gadodiamide (MW ∼573). Magnetic resonance (MR) imaging and videomicroscopy were used to measure the distribution of these infusates, with a simultaneous measurement of infusion pressures. In addition, the forces of catheter penetration and movement through gel and brain were measured. Agarose gel at a 0.6% concentration closely resembles in vivo brain with respect to several critical physical characteristics. The ratio of distribution volume to infusion volume of agarose was 10 compared with 7.1 for brain. The infusion pressure of the gel demonstrated profiles similar in configuration and magnitude to those of the brain (plateau pressures 10–20 mm Hg). Gadodiamide infusion in agarose closely resembled that in the brain, as documented using T1-weighted MR imaging. Gadodiamide distribution in agarose gel was virtually identical to that of BPB dye, as documented by MR imaging and videomicroscopy. The force profile for insertion of a silastic catheter into agarose gel was similar in magnitude and configuration to the force profile for insertion into the brain. Careful insertion of the cannula using a stereotactic guide is critical to minimize irregularity and backflow of infusate distribution. Conclusions. Agarose gel (0.6%) is a useful surrogate for in vivo brain in exploratory studies of convection-enhanced delivery.

N-acetyl-aspartate (NAA) measured by proton nuclear magnetic resonance spectroscopy (1H-NMR) has been used as a marker of neuronal injury in many cerebral pathologies. Therefore, we evaluate the roles of microdialysis vs. 1H-NMR as techniques to assess NAA (NAAd; NAA/Creatine ratio) in the living brain, and compare the results with whole brain NAA (NAAw), analyzed by HPLC after diffuse traumatic brain injury (TBI). Acute (4 h post-injury survival) and late (48 h survival) changes were studied in a sham-operated group (Sham, n = 4), and two injured groups (TBI/4 h, n = 8; TBI/48 h, n = 7). Baseline NAAd was 8.17 +/- 1 microM, and there was no significant difference between groups. There was only a small (twice of control), but transient increase in NAAd in the TBI/4 h group after trauma. Baseline NAA/Cr ratio was 1.35 +/- 0.2, which did not change significantly between baseline, 1, 2, 3, 4 and 48 h or between groups after TBI. Whole brain NAAw (baseline 8.5 +/- 0.5 mmol kg-1 wet weight) did not differ significantly between groups before and after TBI. Diffuse TBI did not produce long-term changes in NAA, assessed by three different methods. These results may indicate that NAA is not a sensitive marker of the severity of diffuse axonal damage. However, further studies are needed to evaluate whether confounding factors such as microdialysis probe, voxel position and non-regional tissue homogenization might have influenced our data.

We measured serial changes in diffusion-weighted magnetic resonance imaging (DW) and in apparent diffusion coefficient (ADC) 1 to 3 hours after induction of acute subdural hematoma (ASDH) in rats, to assess the rate of development of cytotoxic edema and ischemic brain damage observed in this model. Cortical ADC values underneath the hematoma in ASDH rats (n = 12) were significantly lower than those in sham-operated rats (n = 5) at 1 hour. By 3 hours, the area of ADC abnormality had further increased. The lesion areas, as percentage of hemispheric areas on 1- and 3-hour ADC maps, correlated significantly with those on the histologic sections stained with hematoxylin and eosin. The results indicate that DWI with ADC mapping may provide a valuable diagnostic tool for monitoring of early pathologic changes following subdural hematoma in head-injured patients.

✓ The contribution of brain edema to brain swelling in cases of traumatic brain injury remains a critical problem. The authors believe that cellular edema, the result of complex neurotoxic events, is the major contributor to brain swelling and that vasogenic edema, secondary to blood-brain barrier compromise, may be overemphasized. The objective of this study, therefore, was to quantify temporal water content changes and document the type of edema that forms during the acute and late stages of edema development following closed head injury (CHI). The measurement of brain water content was based on magnetic resonance imaging—determined values of tissue longitudinal relaxation time (T1-weighted imaging) and their subsequent conversion to percentage of water, whereas the differentiation of edema formation (cellular vs. vasogenic) was based on the measurement of the apparent diffusion coefficient (ADC) by diffusion-weighted imaging. A new impact-acceleration model was used to induce CHI. Thirty-six adult Sprague—Dawley rats were separated into two groups: Group I, control (six animals); and Group II, trauma (30 animals). Fast ADC measurements (localized, single-voxel) were obtained sequentially (every minute) up to 1 hour postinjury. The T1-weighted images, used for water content determination, and the diffusion-weighted images (ADC measurement with conventional diffusion-weighted imaging) were obtained at the end of the 1st hour postinjury and on Days 1, 3, 7, 14, 28, and 42 in animals from the trauma and control groups. In the animals subjected to trauma, the authors found a significant increase in ADC (10 ± 5%) and brain water content (1.3 ± 0.9%) during the first 60 minutes postinjury. This is consistent with an increase in the volume of extracellular fluid and vasogenic edema formation as a result of blood-brain barrier compromise. This transient increase, however, was followed by a continuing decrease in ADC that began 40 to 60 minutes postinjury and reached a minimum value on Days 7 to 14 (10 ± 3% reduction). Because the water content of the brain continued to increase during the first 24 hours postinjury (1.9 ± 0.9%), it is suggested that the decreased ADC indicated cellular edema formation, which started to develop soon after injury and became dominant between 1 and 2 weeks postinjury. The study provides supportive evidence that cellular edema is the major contributor to posttraumatic swelling in diffuse CHI and defines the onset and duration of the increase in cellular volume.

Primary ciliary dyskinesia (PCD), resulting from defects in cilia assembly or motility, is caused by mutations in a number of genes encoding axonemal proteins. PCD phenotypes are variable, and include recurrent respiratory tract infections, bronchiectasis, hydrocephaly, situs inversus, and male infertility. We generated knockout mice for the sperm-associated antigen–17 (Spag17) gene, which encodes a central pair (CP) protein present in the axonemes of cells with “9 + 2” motile cilia or flagella. The targeting of Spag17 resulted in a severe phenotype characterized by immotile nasal and tracheal cilia, reduced clearance of nasal mucus, profound respiratory distress associated with lung fluid accumulation and disruption of the alveolar epithelium, cerebral ventricular expansion consistent with emerging hydrocephalus, failure to suckle, and neonatal demise within 12 hours of birth. Ultrastructural analysis revealed the loss of one CP microtubule in approximately one quarter of tracheal cilia axonemes, an absence of a C1 microtubule projection, and other less frequent CP structural abnormalities. SPAG6 and SPAG16 (CP proteins that interact with SPAG17) were increased in tracheal tissue from SPAG17-deficient mice. We conclude that Spag17 plays a critical role in the function and structure of motile cilia, and that neonatal lethality is likely explained by impaired airway mucociliary clearance.

Single-walled carbon nanohorns (SWNHs) are new carbonaceous materials. In this paper, we report the first successful preparation of SWNHs encapsulating trimetallic nitride template endohedral metallofullerenes (TNT-EMFs). The resultant materials were functionalized by a high-speed vibration milling method and conjugated with CdSe/ZnS quantum dots (QDs). The successful encapsulation of TNT-EMFs and external functionalization with QDs provide a dual diagnostic platform for in vitro and in vivo biomedical applications of these new carbonaceous materials.

Convection-enhanced delivery (CED) could have clinical application in the delivery of neuroprotective agents following ischemic stroke. However, ischemic brain tissue changes such as cytotoxic edema, in which cellular swelling decreases the fractional volume of the extracellular space, would be expected to significantly alter the distribution of neuroprotective agents delivered by CED. We sought to predict and characterize these effects using the magnetic resonance contrast agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) as a model therapeutic agent. CED was observed using MRI in a normal rat brain and in a middle cerebral artery (MCA) occlusion rat model of brain ischemia. Gd-DTPA was infused to the caudate putamen in the normal rat (n = 6) and MCA occlusion model (n = 6). In each rat, baseline apparent diffusion coefficient images were acquired prior to infusion, and T1 maps were then acquired 13 times throughout the duration of the experiment. These T1 maps were used to compute Gd-DTPA concentrations throughout each brain. In the MCA occlusion group, CED delivered Gd-DTPA to a comparatively larger volume with lower average tissue concentrations. Following the infusion, the total content of Gd-DTPA decreased more slowly in the MCA occlusion group than in the normal group. This quantitative characterization confirms that edematous ischemic tissue changes alter the distribution of agents by CED. These findings may have important implications for CED in the treatment of brain injury, and will assist in future efforts to model the distribution of therapeutic agents.

Water-soluble gadofullerides exhibited high efficiency as magnetic resonance imaging (MRI) contrast agents. In this paper, we report the conjugation of the newly synthesized gadofulleride, Gd@C82O6(OH) 16(-)(NHCH2CH2COOH)8, with the antibody of green fluorescence protein (anti-GFP), as a model for "tumor targeted" imaging agents based on endohedral metallofullerenes. In this model system, the activity of the anti-GFP conjugate can be conveniently detected by green fluorescence protein (GFP), leading to in vitro experiments more direct and facile than those of tumor antibodies. Objective-type total internal reflection fluorescence microscopy revealed that each gadofulleride aggregate conjugated on average five anti-GFPs, and the activity of anti-GFPs was preserved after conjugation. In addition, the gadofulleride/antibody conjugate exhibited higher water proton relaxivity (12.0 mM (-1) s (-1)) than the parent gadofulleride aggregate (8.1 mM (-1) s (-1)) in phosphate buffered saline at 0.35 T, as also confirmed by T1-weighted images of phantoms. These observations clearly indicate that the synthesized gadofulleride/antibody conjugate not only has targeting potential, but also exhibits higher efficiency as an MRI contrast agent.

To evaluate the effectiveness of a functionalized trimetallic nitride endohedral metallofullerene nanoparticle as a magnetic resonance (MR) imaging proton relaxation agent and to follow its distribution for in vitro agarose gel infusions and in vivo infusions in rat brain.The animal study was approved by the animal care and use committee. Gd(3)N@C(80) was functionalized with poly(ethylene glycol) units, and the carbon cage was hydroxylated to provide improved water solubility and biodistribution. Relaxation rate measurements (R1 = 1/T1 and R2 = 1/T2) of water solutions of this contrast agent were conducted at 0.35-, 2.4-, and 9.4-T MR imaging. Images of contrast agent distributions were produced following infusions in six agarose gel samples at 2.4 T and from direct brain infusions into normal and tumor-bearing rat brain at 2.4 T. The relaxivity of a control functionalized lutetium agent, Lu(3)N@C(80), was also determined.Water hydrogen MR imaging relaxivity (r1) for this metallofullerene nanoparticle was markedly higher than that for commercial agents (eg, gadodiamide); r1 values of 102, 143, and 32 L . mmol(-1) . sec(-1) were measured at 0.35, 2.4, and 9.4 T, respectively. In studies of in vitro agarose gel infusion, the use of functionalized Gd(3)N@C(80) at concentrations an order of magnitude lower resulted in equivalent visualization in comparison with commercial agents. Comparable contrast enhancement was obtained with direct infusions of 0.013 mmol/L of Gd(3)N@C(80) and 0.50 mmol/L of gadodiamide in live normal rat brain. Elapsed-time studies demonstrated lower diffusion rates for Gd(3)N@C(80) relative to gadodiamide in live normal rat brain tissue. Functionalized metallofullerenes directly infused into a tumor-bearing brain provided an improved tumor delineation in comparison with the intravenously injected conventional Gd(3+) chelate. A control lutetium functionalized Lu(3)N@C(80) nanoparticle exhibited very low MR imaging relaxivity.The new functionalized trimetallic nitride endohedral metallofullerene species Gd(3)N@C(80)[DiPEG5000(OH)(x)] is an effective proton relaxation agent, as demonstrated with in vitro relaxivity and MR imaging studies, in infusion experiments with agarose gel and in vivo rat brain studies simulating clinical conditions of direct intraparenchymal drug delivery for the treatment of brain tumors.

Object. After traumatic brain injury (TBI), S100B protein is released by astrocytes. Furthermore, cerebrospinal fluid (CSF) and serum S100B levels have been correlated to outcome. Given that no data exist about the temporal profile of cerebral S100B levels following TBI and their correlation to serum levels, the authors examined whether proton magnetic resonance (MR) spectroscopy is capable of measuring S100B. Methods. Results of in vitro proton MR spectroscopy experiments (2.35-tesla magnet, 25 G/cm, point-resolved spatially localized spectroscopy) revealed an S100B-specific peak at 4.5 ppm and confirmed a positive correlation between different S100B concentrations (10 nM–1 µM) and the area under the curve (AUC) for the S100B peak (r = 0.991, p < 0.001). Thereafter, proton MR spectroscopy was performed in male Sprague—Dawley rats (7 × 5 × 5—mm voxel in each hemisphere, TR 3000 msec, TE 30 msec, 256 acquisitions). Exogenously increased CSF S100B levels (∼ 200 ng/ml) through the intraventricular infusion of S100B increased the AUC of the S100B peak from 0.06 ± 0.02 to 0.44 ± 0.06 (p < 0.05), whereas serum S100B levels remained normal. Two hours after lateral fluid-percussion injury, serum S100B levels increased to 0.61 ± 0.09 ng/ml (p < 0.01) and rapidly returned to normal levels, whereas the AUC of the S100B peak increased to 0.19 ± 0.04 at 2 hours postinjury and 0.41 ± 0.07 (p < 0.05) on Day 5 postinjury. Conclusions. Proton MR spectroscopy proves a strong correlation between the AUC of the S100B peak and S100B concentrations. Following experimental TBI, serum S100B levels increased for only a very short period, whereas cerebral S100B levels were increased up to Day 5 postinjury. Given that experimental data indicate that S100B is actively released following TBI, proton MR spectroscopy may represent a new tool to identify increased cerebral S100B levels in patients after injury, thus allowing its biological function to be better understood.

Management of cerebral perfusion pressure (CPP) is thought to be important for the treatment of traumatic brain injury (TBI). Vasopressors have been advocated as a method of increasing mean arterial blood pressure (mABP) and cerebral perfusion pressure (CPP) in the face of rising intracranial pressure (ICP). There are unresolved issues and theoretical risks about this therapy. This study therefore examined the effects of dopamine on physiological and MRI/MRS parameters in (1) a rodent model of rapidly rising intracranial pressure, caused by diffuse injury with secondary insult and (2) a model of cortical contusion. Dopamine was capable of restoring CPP in the model of rapidly rising ICP. This CPP restoration was associated with a partial restoration of CBF. Two profiles of change in the Apparent Diffusion Coefficient of water (ADCw) were seen; one in which ADCw recovered to baseline, and one in which ADCw remained persistently low. Dopamine did not alter these profiles. MRI assessed tissue water content was increased four hours after injury and dopamine increased cerebral water content in both subgroups of injury; significantly in the group with a persistently low ADCw (p0.01). In contusional injury, dopamine significantly worsened edema in both the ipsi- and contralateral hippocampus and temporal cortex. This occurred in the absence of ADCw changes, except in the contralateral hippocampus, where both water content and ADCw values rose with treatment, suggesting extracellular accumulation of water. In conclusion, although dopamine is capable of partially restoring CBF after injury, situations exist in which dopamine therapy worsens the swelling process. It is possible therefore that subgroups of patients exist who experience adverse effects of vasopressor treatment, and consequently the effects of vasopressor therapy in the clinical setting need to be more carefully evaluated.

This work investigates the accuracy of an in vivo estimation of absolute N-acetyl aspartate (NAA) concentrations by magnetic resonance spectroscopy (MRS) using cerebral water as an internal reference standard. Single-voxel, proton spectroscopy was carried out in two groups of rats (normal and diffuse head injury), using a PRESS sequence with TR = 3 s, TE = 135 ms. Fully relaxed water spectra and water-suppressed proton spectra were obtained from a 7 x 5 x 5 mm3 volume of tissue. MRI-based brain water content measurements were also performed. Following MRS, HPLC determinations of NAA were carried out. In the normal rats the MRS yielded 10.98 ± 0.83 mmol/kg w.w. vs 10.76 ± 0.76 for HPLC with a mean absolute difference of 0.8. In the injured rats the corresponding results were 9.41 ± 1.78 (MRS) and 8.16 ± 0.77 (HPLC) with a mean absolute difference of 1.66. The in vivo absolute method accurately documented the temporal NAA changes compared to the NAA/Cr approach.

A one-dimensional time-of-flight MR sequence, having a total acquisition time of approximately 60 ms, has been employed to determine flow-wave propagation velocities for pulsatile flow in compliant latex tubes. The results were compared with those of two independent methods and were found to be in good agreement. An extension of the same MR method was used to test the validity of the "water-hammer" relationship as a means to assess pulse pressure. Very good agreement was found with direct manometric determinations of pulse pressure.

✓ The authors posit that cellular edema is the major contributor to brain swelling in diffuse head injury and that the contribution of vasogenic edema may be overemphasized. The objective of this study was to determine the early time course of blood-brain barrier (BBB) changes in diffuse closed head injury and to what extent barrier permeability is affected by the secondary insults of hypoxia and hypotension. The BBB disruption was quantified and visualized using T1-weighted magnetic resonance (MR) imaging following intravenous administration of the MR contrast agent gadolinium—diethylenetriamine pentaacetic acid. To avoid the effect of blood volume changes, the maximum signal intensity (SI) enhancement was used to calculate the difference in BBB disruption. A new impact-acceleration model was used to induce closed head injury. Forty-five adult Sprague—Dawley rats were separated into four groups: Group I, sham operated (four animals), Group II, hypoxia and hypotension (four animals), Group III, trauma only (23 animals), and Group IV, trauma coupled with hypoxia and hypotension (14 animals). After trauma was induced, a 30-minute insult of hypoxia (PaO2 40 mm Hg) and hypotension (mean arterial blood pressure 30 mm Hg) was imposed, after which the animals were resuscitated. In the trauma-induced animals, the SI increased dramatically immediately after impact. By 15 minutes permeability decreased exponentially and by 30 minutes it was equal to that of control animals. When trauma was coupled with secondary insult, the SI enhancement was lower after the trauma, consistent with reduced blood pressure and blood flow. However, the SI increased dramatically on reperfusion and was equal to that of control by 60 minutes after the combined insult. In conclusion, the authors suggest that closed head injury is associated with a rapid and transient BBB opening that begins at the time of the trauma and lasts no more than 30 minutes. It has also been shown that addition of posttraumatic secondary insult—hypoxia and hypotension—prolongs the time of BBB breakdown after closed head injury. The authors further conclude that MR imaging is an excellent technique to follow (time resolution 1–1.5 minutes) the evolution of trauma-induced BBB damage noninvasively from as early as a few minutes up to hours or even longer after the trauma occurs.

✓ The objective of this study was to use diffusion-weighted magnetic resonance imaging (DWI) to help detect the type of edema that develops after experimental trauma and trauma coupled with hypotension and hypoxia (THH). Reduction in the apparent diffusion coefficients (ADCs) is thought to represent cytotoxic edema. In a preliminary series of experiments, the infusion edema model and middle cerebral artery occlusion models were used to confirm the direction of ADC change in response to purely extracellular and cytotoxic edema, respectively. The ADCs increased (p < 0.05) in the case of extracellular edema and decreased (p < 0.001) in cytotoxic edema.Following these initial experiments, a new impact acceleration model was used to induce traumatic brain injury. Thirty-six adult Sprague-Dawley rats were separated into four groups: sham, trauma alone, hypoxia and hypotension (HH), and THH. Following trauma, a 30-minute insult of hypoxia (PaO2of 40 mm Hg) and hypotension (mean arterial blood pressure (MABP) of 30 mm Hg) were imposed and the animals were resuscitated. The DWI was carried out at four 1-hour intervals postinjury, and MABP, intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebral blood flow (CBF) were monitored. The ADCs in the control and HH groups remained unchanged. The ADCs in the THH group rapidly decreased from a control level of 0.68 ± 0.05 × 10−3mm2/second to 0.37 ± 0.09 3 10−3mm2/second by 3 hours posttrauma (p < 0.001). In this group, the decreased CBF and CPP during secondary insult remained low despite resuscitation, with the ICP increasing to 56 6 7 mm Hg by 3 hours. In the trauma alone group, the rise in ICP reached a maximum value (28 ± 3 mm Hg) at 30 minutes with a significant and sustained increase in CBF despite a gradual decrease in CPP. The ADCs in this group were not significantly reduced. The data lead the authors to suggest that the rise in ICP following severe trauma coupled with secondary insult in this model is predominately caused by cytotoxic edema and that ischemia plays a major role in the development of brain edema after head injury.

not Available.