Sodium MR imaging of acute and subacute stroke for assessment of tissue viability

Sodium MR imaging at 3.0 T provides high-quality images in acceptable acquisition times that allow assessment of tissue viability as defined by maintenance of sodium ion homeostasis. This application is made feasible for clinical stroke evaluation by an efficient projection pulse sequence with extremely short echo time values. This twisted projection imaging provides high signal-to-noise images at adequate resolution (5 x 5 x 5 mm(3)) in less than 10 minutes at 3.0 T. The images are quantified as tissue sodium concentration (TSC) maps that can be interpreted directly in terms of tissue viability. With infarction, baseline TSC values of less than 45 mmol/L increase at variable rates to approximately 70 mmol/L, allowing monitoring of the progression of stroke pathophysiology.     

Xenon CT cerebral blood flow in acute stroke

Acute stroke therapy is evolving rapidly as research moves toward extending the time window for treatment so that more patients can benefit. As physiology-based imaging increasingly is used in patient selection, it is becoming evident that rigid time windows are not applicable to individual patients. Xenon CT has an important role in acute stroke therapeutic intervention as a quantitative, reproducible, rapid, and safe modality, which can provide valuable physiologic data that can optimize patient triage and aid in management.     

Comparative overview of brain perfusion imaging techniques

Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are: Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), Xenon-enhanced Computed Tomography (XeCT), Dynamic Perfusion-computed Tomography (PCT), Magnetic Resonance Imaging Dynamic Susceptibility Contrast (DSC), Arterial Spin-Labeling (ASL), and Doppler Ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow (CBF) or volume (CBV). All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks. This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview, established by consensus among specialists of the various techniques. For clinicians, this paper should offers a clearer picture of the pros and cons of currently available brain perfusion imaging techniques, and assist them in choosing the proper method in every specific clinical setting.     

Acquired middle cranial fossa fistulas: normal pressure and nontraumatic in origin

To the accepted classification of three types of normal pressure, nontraumatic cerebrospinal fluid (CSF) fistulas, we would add "acquired." This type of CSF fistula tends to occur from the middle cranial fossa because of the enlargement of "pitholes" that are normally present in its anterior medial aspect. The enlargement of these bony defects is due to normal intracranial pressure variations that, not uncommonly, create meningoceles and meningoencephaloceles. A portion of the floor of this area is aerated in up to 10% of the normal population by the lateral recess of the sphenoid sinus, the pterygoid recess. Thus, this area has the potential to act as a pathway between the middle fossa and the paranasal sinuses, allowing cerebrospinal fluid to pass into the sinuses. Isotope and computerized tomographic studies are helpful in the localization of such a CSF leak. Tomography of the base of the skull, however, is essential for the ideal definition of possible routes of fistulization. If there is any question of the presence of a middle fossa fistula, these studies can show whether the floor of this area is pneumatized and whether there are any defects in the floor. The treatment of such a fistula should include generalized reinforcement of the floor of the anterior middle fossa by a middle fossa approach. If any doubt exists as to the site of leakage (anterior or middle fossa), the minimal surgical procedure should include exploration of both areas via a frontotemporal craniotomy.     

Fatal rupture of the intracranial carotid artery during transluminal angioplasty for vasospasm induced by subarachnoid hemorrhage. Case report

The authors report the clinical course, radiographic findings, and gross and microscopic pathology of a patient with fatal rupture of the supraclinoid segment of the left internal carotid artery during transluminal angioplasty for subarachnoid hemorrhage-induced vasospasm. The rupture most likely resulted from a small portion of aneurysm neck which remained unclipped, thereby leaving an area of structural weakness in the arterial wall at the site of clipping. The area of structural weakness predisposed the artery to rupture upon the addition of transmural pressure induced by balloon inflation during transluminal angioplasty. Caution is advised when performing transluminal angioplasty in the region of aneurysm clipping since the vessel lumen "recreated" during the clipping procedure may contain some residual and structurally incomplete aneurysm neck in the vessel wall.     

From the Cover: Canine sexual dimorphism in Ardipithecus ramidus was nearly human-like

Body and canine size dimorphism in fossils inform sociobehavioral hypotheses on human evolution and have been of interest since Darwin’s famous reflections on the subject. Here, we assemble a large dataset of fossil canines of the human clade, including all available Ardipithecus ramidus fossils recovered from the Middle Awash and Gona research areas in Ethiopia, and systematically examine canine dimorphism through evolutionary time. In particular, we apply a Bayesian probabilistic method that reduces bias when estimating weak and moderate levels of dimorphism. Our results show that Ar. ramidus canine dimorphism was significantly weaker than in the bonobo, the least dimorphic and behaviorally least aggressive among extant great apes. Average male-to-female size ratios of the canine in Ar. ramidus are estimated as 1.06 and 1.13 in the upper and lower canines, respectively, within modern human population ranges of variation. The slightly greater magnitude of canine size dimorphism in the lower than in the upper canines of Ar. ramidus appears to be shared with early Australopithecus, suggesting that male canine reduction was initially more advanced in the behaviorally important upper canine. The available fossil evidence suggests a drastic size reduction of the male canine prior to Ar. ramidus and the earliest known members of the human clade, with little change in canine dimorphism levels thereafter. This evolutionary pattern indicates a profound behavioral shift associated with comparatively weak levels of male aggression early in human evolution, a pattern that was subsequently shared by Australopithecus and Homo.

A small canine tooth with little sexual dimorphism is a well-known hallmark of the human condition. The small and relatively nonprojecting deciduous canine of the first known fossil of Australopithecus, the Taung child skull, was a key feature used by Raymond Dart for his inference that the fossil represented an early stage of human evolution (1). However, recovery of additional Australopithecus fossils led to the canine of Australopithecus africanus to be characterized as large (compared to that of humans or “robust australopithecines”) and its morphology primitive, based on a projecting main cusp and crown structures lacking or hardly expressed in Homo (2). Later, the perception of a large and primitive canine was enhanced by the discovery and recognition of Australopithecus afarensis and Australopithecus anamensis (3–8), the latter species extending back in time to 4.2 million years ago (Ma). Although assessments of canine size variation and sexual dimorphism in Au. afarensis were hampered by limited sample sizes (9, 10), some suggested that the species had a more dimorphic canine than do humans, equivalent in degree to the bonobo (11) or to chimpanzees and orangutans (12). Initially, Au. anamensis was suggested to express greater canine dimorphism than did Au. afarensis (13, 14). However, based on a somewhat larger sample size, this is now considered to be the case with the tooth root but not necessarily its crown (15–17).Throughout the 1990s and 2000s, a pre-Australopithecus record of fossils spanning >6.0 to 4.4 Ma revealed that the canines of these earlier forms did not necessarily exceed those of Au. afarensis or Au. anamensis in general size (18–28). However, all these taxa apparently possessed canine crowns on average about 30% larger than in modern humans, which makes moderately high levels of sexual dimorphism potentially possible. Canine sexual dimorphism, combined with features such as body size dimorphism, inform sociobehavioral and ecological adaptations of past and present primates, and therefore have been of considerable interest since Darwin’s 1871 considerations (29–57). In particular, the relationship of canine size dimorphism (and/or male and female relative canine sizes) with reproductive strategies and aggression/competition levels in primate species have been a continued focus of interest (14, 33, 35–45, 49–56). Conspecific-directed agonistic behavior in primates related to mate and/or resource competition can be particularly intense among males both within and between groups (14, 44, 57). It is widely recognized that a large canine functions as a weapon in intra- and intergroup incidences of occasional lethal aggression (45, 58–61), and a large, tall canine has been shown or inferred to significantly enhance male fitness (50, 56). Hence, canine size and dimorphism levels in fossil species provide otherwise unavailable insights into their adaptive strategies.Here, we apply a recently developed method of estimating sexual size dimorphism from fossil assemblages of unknown sex compositions, the posterior density peak (pdPeak) method (62), and reexamine canine sexual dimorphism in Ardipithecus ramidus at ∼4.5 Ma. We include newly available fossils recovered from the Middle Awash and Gona paleoanthropological research areas in the Afar Rift, Ethiopia (26, 63, 64) in order to obtain the most reliable dimorphism estimates currently possible. We apply the same method to Australopithecus, Homo, and selected fossil apes, and evaluate canine sexual dimorphism through evolutionary time.We operationally define canine sexual dimorphism as the ratio between male and female means of basal canine crown diameters (the m/f ratio). Because the canines of Ar. ramidus, Au. anamensis, and extant and fossil apes are variably asymmetric in crown shape, we examine the maximum basal dimension of the crown. This can be either the mesiodistal crown diameter or a maximum diameter taken from the distolingual to mesiobuccal crown base (7, 27, 65). In the chronologically later Au. afarensis and all other species of Australopithecus sensu lato and Homo, we examine the more widely available conventional metric of buccolingual breadth, which corresponds to or approximates the maximum basal crown diameter. In anthropoid primates, canine height is more informative than basal canine diameter as a functional indicator of aggression and/or related display (14, 41–44). We therefore also examine available unworn and minimally worn fossil canines with reliable crown heights.     

Advanced CT imaging (functional CT).

Computed tomography can provide anatomic and functional information about the brain. The conventional CT of the brain can be coupled with a cerebral blood flow examination using the stable xenon CT technique and with a CT angiography. Distinct subgroups of patients based on variations in cerebral blood flow and vascular pathology have been demonstrated. The addition of the functional information has become extremely important in triaging and determining the appropriate intervention in the patient with an acute neurological deficit.     

Estimating sexual size dimorphism in fossil species from posterior probability densities

Accurate characterization of sexual dimorphism is crucial in evolutionary biology because of its significance in understanding present and past adaptations involving reproductive and resource use strategies of species. However, inferring dimorphism in fossil assemblages is difficult, particularly with relatively low dimorphism. Commonly used methods of estimating dimorphism levels in fossils include the mean method, the binomial dimorphism index, and the coefficient of variation method. These methods have been reported to overestimate low levels of dimorphism, which is problematic when investigating issues such as canine size dimorphism in primates and its relation to reproductive strategies. Here, we introduce the posterior density peak (pdPeak) method that utilizes the Bayesian inference to provide posterior probability densities of dimorphism levels and within-sex variance. The highest posterior density point is termed the pdPeak. We investigated performance of the pdPeak method and made comparisons with the above-mentioned conventional methods via 1) computer-generated samples simulating a range of conditions and 2) application to canine crown-diameter datasets of extant known-sex anthropoids. Results showed that the pdPeak method is capable of unbiased estimates in a broader range of dimorphism levels than the other methods and uniquely provides reliable interval estimates. Although attention is required to its underestimation tendency when some of the distributional assumptions are violated, we demonstrate that the pdPeak method enables a more accurate dimorphism estimate at lower dimorphism levels than previously possible, which is important to illuminating human evolution.

Sexual dimorphism across primates and in humans has been investigated to elucidate its evolutionary significance. Particular attention has been paid to body, skeletal, and canine size dimorphism. This is because of suggested relationships of these dimorphisms with ecological and sociobehavioral variables, especially in relation to reproductive behavior, and also because these parameters can be assessed in fossil assemblages (see refs. 1–3 for relatively recent overviews). Following the influential work of Clutton-Brock et al. (4), the ratio between male and female mean sizes (or its logarithm) (5, 6) has been the predominant parameter used in quantifying sexual size dimorphism, a simple, but fundamental, parameter in assessing adaptive strategies. In this paper, we refer to this measure as the “m/f ratio.” Although this ratio is straightforwardly determinable in extant species and populations, this is not the case in fossils because the sex of a specimen is generally unknown.In estimating the m/f ratio from fossil assemblages with no sex information, a commonly applied method is the “mean method” (here abbreviated the “MM”) (7), which splits the sample into two subgroups, one above and the other below the sample mean. The ratio between the two subgroup means is considered the m/f ratio. In other words, the assumption is made that all specimens larger than the sample mean are males, and vice versa for females. This assumption would be reasonable only when the distributions of the two sexes overlap minimally, which is not necessarily the case in many features or taxa of interest. In estimating overall skeletal size dimorphism, a multivariate version of the MM has also been suggested (6). In this method, the m/f ratio is calculated as the geometric mean of the m/f ratios of multiple skeletal elements, thereby enabling dimorphism estimates from larger fossil sample sizes. However, caution is needed when partial skeletons are included in the analysis, because the dimorphism estimate can be weighted by relatively few individuals. This may result in a highly biased estimate, as in the case of the Australopithecus afarensis skeletal size dimorphism (6, 8).Rather than accepting the assumption that the two sexes segregate at the mean, Lovejoy et al. (9) proposed a method that takes into account the unknown sex status of the specimens. Supposing a sample of N specimens, there are N − 1 possible splitting points between males and females and an equal number of possible m/f ratio values. Then, assuming equal chance of the two sexes being represented in the fossil sample, the m/f ratio is calculated by weighing the N − 1 presumed male-to-female ratios with their binomial probabilities. This method was later termed the binomial dimorphism index (here, the “BDI”) (10). When there is large size overlap between the sexes, this procedure is expected to correct for bias stemming from allocating sex via the sample mean. However, it shares with the MM the assumption that all males are larger than all females, and it has been shown (as with the MM) to overestimate weak skeletal size dimorphism, such as in chimpanzees (6, 10).Another approach for estimating dimorphism is to use the empirical correlation observed between the m/f ratio and the coefficient of variation (CV; the SD divided by the mean). In traits that show a range of size dimorphism levels among taxa or populations, there is a strong tendency of a larger total CV to be associated with a larger m/f ratio. Using such a relationship, the m/f ratio of fossils can be estimated (11) via regression using known-sex extant samples (12–14) or simulated data (15, 16). However, as demonstrated in validation studies (15, 17), the CV method (hereafter, the “CVM”) is susceptible to within-sex CV (hereafter, “wsxCV”) levels and can overestimate, especially when sexual dimorphism is weak to moderate, as do the MM and BDI. This is because, when the two sex distributions substantially overlap, it is difficult to distinguish whether a large total CV stems from large sexual size dimorphism or large within-sex variance, the latter generally unknown in fossil assemblages.Here, we introduce the “posterior density peak” (hereafter “pdPeak”) method , a method of estimating the m/f ratio in fossil assemblages of unknown sex via a Bayesian mixture model. We model the background population from which the fossil sample is derived by three parameters, the male and female means and the common within-sex variance (all in log scale). Applying the Bayes theorem, we assign probabilities to the combinations of these three parameters that realize the sample distribution in hand. By this method, the distance between the two subgroups (dimorphism level) and within-subgroup variation can be evaluated simultaneously in terms of the fit of the model to a given sample distribution. In other words, “shape ” of the sample distribution is considered when estimating size dimorphism. Fig. 1 illustrates how a population with the same total variation (combined-sex CV) can contain divergent latent distributions with a range of m/f ratios and within-sex variances, resulting in entirely different overall distributional shapes. It is clear that distribution shape is important in inferring distance (dimorphism) between subgroup means. We show that our method resolves the m/f ratio better than the other methods when male–female distributions overlap substantially.Open in a separate windowFig. 1.Variation in shape of population distributions with a constant CV of 10%. (A–D) Hypothetical population (combined-sex) distributions with the same overall variation (CV of 10%) are plotted for several subgroup conditions. Log-normal distributions of males and females with a common wsxCV are mixed in equal proportions. Overall CV is fixed at 10% and the female mean at 10 mm. The wsxCV is set in four ways: 8%, 7%, 6%, and 5% (from left to right). Solid black curves indicate overall distributions, dashed curves are the latent within-sex distributions, red is for female, and blue is for male. Vertical dashed lines indicate within-sex means. The same distributions are shown in E–H segregated to subpopulations by the mean. Vertical solid lines indicate the presumed sex means of the mean method (MM). The true male mean/female mean (m/f ratio), as well as the MM ratio (mean of presumed males divided by that of the presumed females), is shown below each wsxCV condition. Note that the MM increasingly overestimates as the male and female distributions increasingly overlap (from right to left). The Rd values (see Application to Actual Cases), i.e., the distance between means in within-sex SD units, are 1.6, 2.2, 2.9, and 3.8, respectively in A, B, C, and D. Note also that, under the same overall CV, the true m/f ratio can vary substantially depending on wsxCV.We present the pdPeak method and evaluate its performance by 1) using computer-generated samples from simulated populations and 2) applying the method to a large dataset of extant anthropoid canine crown metrics of known sex. We compare the pdPeak method with the other most commonly used methods, the MM, BDI, and CVM. Lastly, we apply the pdPeak method to an actual sample of fossil canines to explore its potential in human evolutionary studies.In evaluating the pdPeak method, we focus on canine crown size for simplicity. The canine crown diameter m/f ratios seen in the extant great apes and modern humans are summarized in SI Appendix, Table S1. In extant great apes, the m/f ratio ranges from ∼1.2 to ∼1.5. The most dimorphic is the gorilla, with maximum canine crown diameter m/f ratios of ∼1.4 to 1.5. The same ratios of chimpanzees and orangutans range from ∼1.2 to 1.4, with the least dimorphism seen in the bonobo lower canine (13, 18–22). To the contrary, in humans, the m/f ratio of canine crown diameters varies among populations, predominantly between 1.03 and ∼1.10 (23). Based on this, we focus on discerning m/f ratios of the 1.1 to 1.2 interval, the range bridging the extant great ape and human conditions.