Aging alters patterns of regional nonuniformity in LV strain relaxation: a 3-D MR tissue tagging study

Although age-related impairment of diastolic function is well documented, patterns of regional tissue relaxation impairment with age have not been characterized. MRI tissue tagging with a regional three-dimensional (3-D) analysis was performed in 15 younger (age 19-26 yr) and 16 older (age 60-74 yr) normal, healthy volunteers. The peak rate of relaxation of circumferential strain (RC) was decreased in the older group (on average, 105 +/- 28 vs. 163 +/- 18 %/s for older vs. younger, mean +/- SD, P < 0.001) to a greater extent in the lateral wall than in the septum (P = 0.016) and to a greater extent in the apex than in the base (P < 0.001). Peak rate of relaxation of longitudinal strain (RL) was also reduced with age (94 +/- 27 vs. 155 +/- 18 %/s, P < 0.001) to a greater extent in the apex than in the base (P < 0.001). Both RC and RL were greater in the apex than in the base only in the younger subjects (P < 0.001 for each). Peak rate of torsion reversal (RT) was reduced with age (74 +/- 16 vs. 91 +/- 15 degrees/s, P = 0.006) to a greater extent in the base than in the apex (P = 0.035). An increase in regional asynchrony in time to RC and time to RL (P < 0.001 for each), but not time to RT, occurred with age. Thus patterns of regional nonuniformity of myocardial relaxation are altered in a consistent fashion with aging.     

MRI assessment of LV relaxation by untwisting rate: a new isovolumic phase measure of tau

Most noninvasive measures of diastolic function are made during left ventricular (LV) filling and are therefore subject to "pseudonormalization," because variation in left atrial (LA) pressure may confound the estimation of relaxation rate. Counterclockwise twist of the LV develops during ejection, but untwisting occurs rapidly during isovolumic relaxation, before mitral opening. We hypothesized that the rate of untwisting might reflect the process of relaxation independent of LA pressure. Recoil rate (RR), the velocity of LV untwisting, was measured by tagged magnetic resonance imaging and regressed against the relaxation time constant (tau), recorded by catheterization, in 10 dogs at baseline and after dobutamine, saline, esmolol, and methoxamine treatment. RR correlated closely (average r = -0.86) with tau and was unaffected by elevated LA pressure. Multiple regression showed that tau, but not LA or aortic pressure, was an independent predictor of RR (P < 0.0001, P = 0.99, and P = 0.18, respectively). The rate of recoil of torsion, determined wholly noninvasively, provides an isovolumic phase, preload-independent assessment of LV relaxation. Use of this novel parameter should allow the detailed study of diastolic function in states known to affect filling rates, such as aging, hypertension, and congestive heart failure.     

Timing of cardiac contraction in humans mapped by high-temporal-resolution MRI tagging: early onset and late peak of shortening in lateral wall

Mechanical asynchrony is an important parameter in predicting the response to cardiac resynchronization therapy, but detailed knowledge of cardiac contraction timing in healthy persons is scarce. In this work, timing of cardiac contraction was mapped in 17 healthy subjects with high-temporal-resolution (14 ms) MRI myocardial tagging and strain analysis. Both the onset time of circumferential shortening (T(onset)) in early systole and the time of peak circumferential shortening (T(peak)) at end systole were determined. The onset of shortening width (time needed for 20-90% of the left ventricle to start shortening) was small (35 +/- 9 ms). A distinct spatial pattern for T(onset) was found, with earliest onset in the lateral wall and latest onset in the septum (P = 0.001). Compared with T(onset), T(peak) had a larger width (121 +/- 22 ms) and an opposite spatial pattern, with peak shortening occurring earlier in the septum than in the lateral wall (P < 0.001). Postsystolic shortening (T(peak) later than aortic valve closure; P < 0.05) was observed in 13 of the 30 cardiac segments, mainly in the lateral and basal segments. Shortening in these segments continued 58 +/- 14 ms after aortic valve closure, during which circumferential shortening increased from 16.9 +/- 1.2% to 20.0 +/- 1.5%. Maps of the timing of contraction in normal subjects may serve as a reference in detecting mechanical asynchrony due to intraventricular conduction defects or ischemia.     

3-D MRI assessment of regional left ventricular systolic wall stress in patients with reperfused MI

The goal of this study was to assess the regional variations of end-systolic wall stress in patients with reperfused Q wave acute myocardial infarction (AMI), with the use of a three-dimensional (3-D) approach. Fifteen normal volunteers and fifty patients with reperfused AMI underwent cardiac MRI that used a short-axis fast-gradient-echo sequence. The end-systolic wall stress was calculated with the use of the Grossman formula with the radius and the wall thickness defined with a 3-D approach using the tridimensional curvature. The mean wall stress was significantly increased at each level of the short-axis plane only in patients with anterior AMI. When calculated at a regional level in patients with anterior AMI, wall stress significantly increased in anterior sector as well as normal sector. In patients with inferior AMI, wall stress significantly increased only in inferior and lateral sectors. In conclusion, the quantification of regional wall stress by cardiac MRI is better with the 3D approach than other methods for precise evaluation in patients with AMI. Despite early reperfusion, the wall stress remained high in patients with anterior AMI.     

实时三维超声心动图评价房间隔缺损患者手术前后心室收缩功能

目的 应用实时三维超声心动图(RT-3DE)研究房间隔缺损(ASD)患者行内科介入手术前后左、右室心肌收缩变化的相关关系.方法 应用RT-3DE技术对34例ASD患者术前、术后1周以及35例正常受检者(对照组)的左、右室舒张末期容量(LVEDV/RVEDV),左、右室收缩末期容量(LVESV/RVESV),左、右室每搏量(LVSV/RVSV)及左、右室射血分数(LVEF/RVEF)进行统计分析.结果 术前,ASD患者LVEDV、LVSV、LVEF均小于对照组(均P＜0.05),RVEDV、RVESV、RVSV、RVEF均大于对照组(均P＜0.05);术后1周内,ASD患者LVEDV、LVSV、LVEF均较术前增大(均P＜0.05),RVEDV、RVSV、RVEF均较术前减小(均P＜0.05);ASD患者术后的LVEDV、LVESV、LVSV、LVEF与对照组比较均无统计学意义(均P＞0.05),而RVEDV、RVESV、RVSV均大于对照组(P＜0.05);ASD患者术后左、右室的射血分数变化之间均无相关性.结论 行内科介入的ASD患者术后初期左、右室收缩功能即恢复到正常水平,术后左、右室射血分数的变化之间均无相关性.     

LV systolic performance improves with development of hypertrophy after transverse aortic constriction in mice

Transverse aortic constriction (TAC) is an effective technique for inducing left ventricular (LV) hypertrophy in mice. With the use of transthoracic echocardiography and Doppler measurements, we studied the effects of an acute increase in pressure overload on LV contractile performance and peak systolic wall stress index (WSI) at early time points after TAC and the time course of the development of LV hypertrophy in mice. The LV mass index was similar between TAC and sham-operated mice at postoperative day 1 but progressively increased in TAC mice by day 10. There was no further increase in the LV mass index between postoperative days 10 and 20. On day 1, whereas peak systolic WSI increased significantly, the LV ejection fraction (LVEF) and percent fractional shortening (%FS) decreased in TAC mice compared with sham-operated mice. By day 10, peak systolic WSI, LVEF, and %FS had recovered to baseline levels and were not significantly different between postoperative days 10 and 20. Thus LV systolic performance in mice declines immediately after TAC, associated with increased peak systolic WSI, but recovers to baseline levels with the development of compensatory LV hypertrophy over 10-20 days.     

Late replicating bands of human chromosomes demonstrated by fluorochrome and Giemsa staining.

The addition of thymidine (TdR) to cells growing in a medium containing 5-bromodeoxyuridine (BUdR) at the end of the first replication cycle results in the incorporation of TdR into the late replicating DNA regions. These sites can be visualized by staining the metaphase chromosomes with the fluorescent dye "33258 Hoechst" or a "33258 Hoechst" Giemsa procedure. A sequence of late replication patterns has been established in metaphase chromosomes of cultured human peripheral lymphocytes. The patterns are in agreement with those obtained by the standard autoradiographic procedures, but are more accurate. As is known from autoradiography, late replicating bands are in the position of G or Q bands. The "33258 Hoechst" Giemsa staining procedure of chromosomes which have replicated in the presence of BUdR first and in TdR for the last 2 hrs of the S phase is preferable to the currently used Giemsa banding techniques: the method yields very well banded metaphases in all preparations examined, as the chromosome structure is not disrupted by the pretreatment. The bands are very distinct, even in the "difficult" chromosomes (e.g. No. 4, 5, 8 and X). In female cells the late replicating X chromosome can be identified by its size and staining pattern. In addition to the replication asynchrony, the sequence of replication within both X chromosomes in female cells is not absolutely identical. The phenomenon of a phase difference in replication between the homologues is not a peculiarity of the X chromosome, but can be found in all autosomes as well as in homologous positions on the chromatids of individual chromosomes.     

Analysis of tissue responses to fin tagging in Australian carcharhinids

Tissue responses to the application of Rototags and Jumbo Rototags in the first dorsal fin of Carcharhinus melanopterus, C. obscurus and C. plumbeus were examined. The acute response included tissue tearing and haemorrhage and was present by 5 days post-tagging. The intermediate response had begun by 20 days post-tagging and continued beyond 207 days. This response involved decreased red blood cell activity as the inflammatory response commenced. The chronic response had begun by 301 days and was complete by 553 days with a layer of fibrous connective tissue walling off the tag. External damage to the fin was caused by continued abrasion by the tag. Repair scales were observed at 242 days using scanning electron microscopy and were confirmed histologically in 61- and 553-day samples. Repair scales were not seen in areas of continuous abrasion. No infection was observed in tissues surrounding the wound. Disruption of the fin surface was observed due to abrasion by the tag, but did not appear to cause a severe tissue reaction. The tissue responses observed were consistent with a normal, but relatively slow, healing in the vicinity of the tag wound. Use of Rototags or Jumbo Rototags appears to be an efficient way of marking elasmobranchs with minimal damage to the shark.     

The three-dimensional reticular structure of the pig spleen demonstrated by labelling with fluorescein isothiocyanate

Summary Pig spleens were selectively perfused with a fluorescein isothiocyanate (FITC) containing medium. Histological sections of spleens excised one day later revealed the structure of the reticulum in thick cryostat sections directly in three dimensions. The pattern of the reticulum in silver impregnated sections was comparable to the FITC labelling pattern. This technique preferentially outlines the reticulum of the white pulp and the marginal zone of the spleen.Partly presented at the 6th Europ. Anat. Congr., Hamburg, Sept. 81, Acta Anat. 111, 109, 1981We are grateful to Ms. M. Kaatz and H. Wilting and to Mr. I. King and J. Jarvis for preparing the histological sections and Mr. R. Gallup for the photographs and to Sheila Fryk for secretarial assistanceThis study was partly supported by the Deutsche Forschungsgemeinschaft (Pa 240/2)     

Diastolic suction is impaired by bed rest: MRI tagging studies of diastolic untwisting.

Bed rest deconditioning leads to physiological cardiac atrophy, which may compromise left ventricular (LV) filling during orthostatic stress by reducing diastolic untwisting and suction. To test this hypothesis, myocardial-tagged magnetic resonance imaging (MRI) was performed, and maximal untwisting rates of the endocardium, midwall, and epicardium were calculated by Harmonic Phase Analysis (HARP) before and after -6 degrees head-down tilt bed rest for 18 days with (n = 14) and without exercise training (n = 10). LV mass and LV end-diastolic volume were measured using cine MRI. Exercise subjects cycled on a supine ergometer for 30 min, three times per day at 75% maximal heart rate (HR). After sedentary bed rest, there was a significant reduction in maximal untwisting rates of the midwall (-46.8 +/- 14.3 to -35.4 +/- 12.4 degrees /s; P = 0.04) where untwisting is most reliably measured, and to a lesser degree of certainty in the endocardium (-50.3 +/- 13.8 to -40.1 +/- 18.5 degrees /s; P = 0.09); the epicardium was unchanged. In contrast, when exercise was performed in bed, untwisting rates were enhanced at the endocardium (-48.4 +/- 20.8 to -72.3 +/- 22.3 degrees /ms; P = 0.05) and midwall (-39.2 +/- 12.2 to -59.0 +/- 19.6 degrees /s; P = 0.03). The differential response was significant between groups at the endocardium (interaction P = 0.02) and the midwall (interaction P = 0.004). LV mass decreased in the sedentary group (156.4 +/- 30.3 to 149.5 +/- 27.9 g; P = 0.07), but it increased slightly in the exercise-trained subjects (156.4 +/- 34.3 to 162.3 +/- 40.5 g; P = 0.16); (interaction P = 0.03). We conclude that diastolic untwisting is impaired following sedentary bed rest. However, exercise training in bed can prevent the physiological cardiac remodeling associated with bed rest and preserve or even enhance diastolic suction.     

Apoptosis in lactating and involuting mouse mammary tissue demonstrated by nick-end DNA labelling

Mammary involution after cessation of milk removal is associated with extensive loss of secretory epithelial cells. Ultrastructural changes and the appearance of oligonucleosomal DNA laddering in ethidium bromide-stained gels indicates that cell loss during involution occurs by apoptosis. In this study, a technique for nick end-labelling of genomic DNA with radiolabelled deoxynucleotide has been used to monitor the induction of programmed cell death in mice after litter removal at peak lactation. This technique proved more sensitive than conventional ethidium bromide staining, and results suggested that apoptosis was induced rapidly by milk stasis, before extensive tissue re-modelling had begun. Oligonucleosomal DNA laddering on agarose gels was detected within 24 h of milk stasis, and increased progressively for at least 4 days. Nick-end labelling also detected laddering before litter removal, suggesting that programmed cell death is a normal feature of the lactating tissue. The DNA end-labelling technique was also adapted for in situ visualisation of apoptotic cells in tissue sections. By this criterion, apoptotic cells were identified in both the secretory epithelium lining the alveoli of the gland and, increasingly with prolonged milk stasis, amongst those sloughed into the alveolar lumen. The results demonstrate the utility of these techniques for study of mammary cell death and suggest that, whilst apoptosis is rapidly induced by milk stasis, it is also a normal physiological event in the lactating mammary gland.     

Invasion of mesenchyme into three-dimensional collagen gels: a regional and temporal analysis of interaction in embryonic heart tissue

In normal heart development the endothelium of the atrioventricular canal, but not the ventricle, produces mesenchymal cells which seed (invade) into the intervening extracellular matrix toward the myocardium at around 64-69 hr of development. We have utilized three-dimensional collagen substrates to examine the initiation of seeding by atrioventricular canal endothelia in vitro and to compare and contrast the responses of the ventricular endothelia. Explants of atrioventricular canals and ventricles from staged embryos were placed on the surfaces of collagen gels prior to the onset of seeding in situ. At varied intervals of incubation, the explant was removed, leaving behind a monolayer on the surface of the gel which consisted of endothelial cells. Subsequently, the endothelial outgrowths were examined for seeded cells. The results confirm the regional endothelial differences seen in vivo. They also show that invasion of the collagen gels is due to an alteration in phenotype mediated by interaction with other components of embryonic heart explant. Lastly, the time course of this tissue interaction in vitro mimics the onset of seeding in vivo.     

Late onset of motor neurons in mice overexpressing wild-type peripherin

Peripherin, a type III intermediate filament (IF) protein, upregulated by injury and inflammatory cytokines, is a component of IF inclusion bodies associated with degenerating motor neurons in sporadic amyotrophic lateral sclerosis (ALS). We report here that sustained overexpression of wild-type peripherin in mice provokes massive and selective degeneration of motor axons during aging. Remarkably, the onset of peripherin-mediated disease was precipitated by a deficiency of neurofilament light (NF-L) protein, a phenomenon associated with sporadic ALS. In NF-L null mice, the overexpression of peripherin led to early- onset formation of IF inclusions and to the selective death of spinal motor neurons at 6 mo of age. We also report the formation of similar peripherin inclusions in presymptomatic transgenic mice expressing a mutant form of superoxide dismutase linked to ALS. Taken together, these results suggest that IF inclusions containing peripherin may play a contributory role in motor neuron disease.     

Transmural gradients of cardiac myofiber shortening in aortic valve stenosis patients using MRI tagging

Aortic valve stenosis impairs subendocardial perfusion with a risk of irreversible subendocardial tissue damage. A likely precursor of damage is subendocardial contractile dysfunction, expressed by the parameter TransDif, which is defined as epicardial minus endocardial myofiber shortening, normalized to the mean value. With the use of magnetic resonance tagging in two short-axis slices of the left ventricle (LV), TransDif was derived from LV torsion and contraction during ejection. TransDif was determined in healthy volunteers (control, n = 9) and in patients with aortic valve stenosis before (AVSten, n = 9) and 3 mo after valve replacement (AVRepl, n = 7). In the control group, TransDif was 0.00 +/- 0.14 (mean +/- SD). In the AVSten group, TransDif increased to 0.96 +/- 0.62, suggesting impairment of subendocardial myofiber shortening. In the AVRepl group, TransDif decreased to 0.37 +/- 0.20 but was still elevated. In eight of nine AVSten patients, the TransDif value was elevated individually (P < 0.001), suggesting that the noninvasively determined parameter TransDif may provide important information in planning of treatment of aortic valve stenosis.     

Representation of three-dimensional visual space in the cerebral cortex

This article reviews two issues relevant to the topic of how three-dimensional space is represented in the cerebral cortex. The first is the question of how individual neurons encode information that might contribute to stereoscopic estimation of visual depth. Particular attention is given to the current understanding of the neural representation of motion through three-dimensional space and to the complexities that arise in interpreting neuronal responses to this complex stimulus parameter. The second issue considered is the disorderlines that exists in the retinotopic mapping of the visual field in some cortical visual areas. Several extrastriate areas have been found to contain maps of the contralateral visual hemifield that are disorderly in the sense that the representation of various parts of the visual field are often misplaced or grossly over-or under-represented. It is suggested that this disorderlines may in some cases represent adaptations to facilitate certain types of visual functions.