As shown in Tables 5 and 6, the calibers of arteriolar limb, curved segment, and venular limb of capillary for normal subjects are all smaller than the patients with hypertension. It can be explained by that increased blood pressure tends to cause capillary dilation, which damages end-organ sites and leads to hypertension, proteinuria, and edema (Jerath et al. 2009). Contrast to the capillary, inward eutrophic remodeling of resistance vasculature of small arteries is manifested as reduced lumen, an increase of ratio of media width to lumen diameter, and constant media cross-sectional area for patients with essential hypertension (For review, see Feihl et al. 2008, Mulvany 2008, Rizzoni and Agabiti-Rosei 2011). Inward eutrophic remodeling were also found in retinal small arteries in
hypertensive patients (Lehmann and Schmieder 2011). Our data obtained from nail-fold capillaries demonstrate a slight increase of capillary diameter for hypertensive patients; however, significant difference between the normal subjects and hypertensive patients is not observed (t-test, p>0.05), which is consistent to the result obtained by de Araújo Penna et al. (2008). Different muscular characteristics between the subcutaneous small arteries and cutaneous capillaries might be the reason causing such a variation.
The average blood flow velocity for the hypertensive patients is significantly lower than the normal subjects (t-test, p<0.01), as indicated in Tables 5 and 6. This finding again is consistent to the experimental result of de Araújo Penna et al. (2008). Recently, patients with systemic sclerosis were also reported to have significant decrease in blood flow velocity compared to healthy controls (Mugliet al. 2009). On the other hand, it was reported that after 3 months of active treatment of anti-hypertension medication Enalapril, an angiotensin-converting enzyme inhibitor (ACE), for patients with mild-to-moderate hypertension the blood flow velocity, the blood flow velocity increased significantly (p<0.005) immediately after local cooling (Martina et al. 1999). It mimics the effectiveness of the Enalapril in treating hypertention by improving the capillary hemodynamics.
The PTVNMHA proposed in this paper can automatically perform motion compensation, capillary identification, morphological/hemodynamic features extraction and pseudo three-dimensional blood flow visualization from a nail-fold microcirculation image sequence. The morphological/hemodynamic features derived are significant pathological indicators for many diseases, such as hypertension, anemia, diabetes and microcirculation lesion. Although Laser
Doppler flowmetry has been used to measure vasomotion from the flowmotion of blood, it is not vessel specific and cannot be used to detect vasomotions of individual arterioles (Salerud et al. 1983, Koutsiaris et al. 2010). Hence, compared with the laser Doppler velocimetry that can only estimate the average and instantaneous blood velocity and perfusion within the sampling area (Struijker-Boudier et al. 2007), PTVNMHA is capable of measuring the blood flow velocity and blood flow rate of every capillary located across the observed microscopic area separately with a higher precision and lower equipment setup cost. Pseudo 3D animated blood flow visualization is a powerful diagnostic tool allowing the observation of capillaries in any orientation, magnification and viewpoint desirable. The automatic extraction of structural and functional features of capillaries can provide objective and reliable morphological/hemodynamic information and have the potential to facilitate studies relevant to the temporal progression of microvascular diseases, e.g., microangiopathy, peripheral vascular disease (PVD) or diabetic neuropathy, or the finding of a significant index for a specific disease through the automatic analysis of a large amount of microvascular images. The proposed PTVNMHA can be easily adapted to derive a diversity of quantities such as aggregate capillary length, capillary hematocrit and red blood cell spacing, when the needs arise- a unique characteristic unmatchable by other existing methods or equipments. The precision of the features obtained will also keep improving as the resolution of the image capturing device increases. The limitation of this study is that only five patients with hypertension and one patient with anemia were recruited for the measurement of morphological and hemodynamic features. More patients with cardiovascular diseases are needed to be tested to confirm the findings of this study in the future.
In conclusion, the contributions of this study are as follows: (1) Contrast to the previous studies (Wu et al. 2009, Shih et al. 2011), the PTVNMHA system developed provides not only the functions to calculate hemodynamic features but also the operations to calculate morphological features. (2) As reported by de Araújo Penna et al. (2008), the evidence that average blood flow velocity of the hypertensive patients is significantly lower than the normal subjects has been further confirmed in
this study. (3) In addition to blood flow velocity, the blood flow rate has also been proposed and demonstrated to be a useful feature for discriminating the hypertensive patients from the normal.
Contrast to the blood flow velocity, blood flow rate is very uniform in different positions of a capillary, which can be measured much easier than the blood flow velocity calculated in various capillary positions with different values (Shih et al. 2011) . Blood flow rate is superior to the blood flow velocity in the diagnosis of suspected patients with mild hypertension before deteriorating.
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