The COVID-19 pandemic has provided some serious challenges to performing research over the better part of the last 2 years, but despite the hurdles it has presented, noteworthy findings continue to emerge. One such study that I would like to highlight is a recent publication by Franken et al, who present their results using x-ray videocystoscopy for high-speed monitoring of lower urinary tract function in mice with and without mechanical or pharmacological challenges (in fact, this is nearly the exact title of the article).¹ Their findings are exciting, as they push the envelope of animal research insofar as obtaining higher precision and understanding of independent physiological measurement outcomes when performing urodynamic studies in animal models. As my colleague Dr. Phillip P. Smith, MD (UConn Health), who alerted me to this article’s existence, wrote in his email, “There is now a new standard to meet.” But there is more to the story.

Before we discuss the more physiological, rather than technological, significant findings presented in the article by, let’s take a moment for silent meditation on the decline of urodynamics and the even greater under-utilization of videourodynamics in clinical research/diagnostics. Videourodynamics is arguably the best currently available approach for clinical diagnostic physiology in patients,² but the costs and invasive nature of this, and even regular urodynamics, have led to the adoption of largely symptom-based diagnoses. Moreover, because there has been relatively little effort to sub-phenotype patient populations that exist within the super-family syndromic classifications of many so-called benign urological “diseases” (such as idiopathic overactive and underactive bladder), it is not surprising that, given limited therapeutic mechanism of action options, urodynamics may be viewed as less than useful in directing treatment unless invasive treatments are to be employed.^3,4 Movement toward personalized medicine is less rapid and robust in benign disease than in oncology. The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has been tasked with parsing out pathophysiological sub-phenotypes of such symptom-based groupings,⁵ and we eagerly await their findings.

As further background, it is important to note that both decentralized and fully innervated bladders may demonstrate modular (and, in the case of decentralized, autonomous) activity not directly related to parasympathetic output,^6-8 but nonetheless sensed regardless of whether they result in an intraluminal pressure increase.⁸ The latter finding supports the notion that conventional urodynamics may not adequately address the existence of modular, regionally uncoordinated urodynamically “silent” detrusor overactivity, although it is certainly capable of detecting regionally coordinated detrusor overactivity (ie overactivity that is capable of creating pressure increases). Nonetheless, the source of the pressure increase in urodynamically detected detrusor overactivity cannot be ascertained without videourodynamic approaches. In fact, calling an unintentional, uninhibited pressure rise “detrusor overactivity” assumes that the source of the contraction resulting in the pressure rise is, in fact, the detrusor.

Although it is often the case that the bladder and urethra are conceptualized (and therefore treated) as a balloon and a straw, respectively, especially when biomechanical considerations are being discussed, it is well recognized that there are regional differences in the anatomy and function of the functional unit.⁹ We had previously found, utilizing a very primitive approach of time-lapse video photography that did not lend itself readily to quantification, that the bladder base of rats could be visualized to contract in a peristaltic-like manner toward the base following injection of urine from both ureters.¹⁰ These contractions were coincident with the typical low amplitude myogenic contractions that occur during filling in this species.

We hypothesized that these base-to-dome contractions, coordinated in time following bilateral urine injection from the ureters, serve to aid in bladder filling, working against the basal smooth muscle tone of the dome to inflate it. We later found that the frequency of these rhythmic filling contractions was independent of the duration of bladder fill time (manipulated in opposite directions by bladder irritation and sacral neuromodulation),¹¹ supporting the notion that the ureteric activity, driven by the kidneys, was responsible for timing these bladder filling contraction events. I was, therefore, quite excited to see the paper by Franken et al,¹ not only for the technological leap that it represents in quantifiable rodent videocystometric evaluation, but as it also verified our unquantified observation of bladder base contraction as the source of the rhythmic contractions observable in rodents during bladder filling.

This fundamental concept, that the bladder base aids in bladder filling, is important for our understanding of lower urinary tract physiology, and demonstrates that we should not rely solely on symptoms, but should, in a perfect world, leap toward videocystometric techniques for understanding the pathophysiologies that we wish to treat as well as the potential effects on physiological functioning systems previously unknown and/or not considered. For example, is this directional filling mechanism important in humans? I am not sure that anyone has looked properly to determine whether this is the case (ie may require a lateral view to detect). Might such information affect our choice for therapeutic intervention? Certainly. Antimuscarinics target parasympathetic-dependent overactivity, while β3-adrenergic receptor agonists may be treating bladder base or otherwise parasympathetic-independent activity. Knowing which one you are dealing with will allow you to better direct treatment. Other questions come to mind. One that we asked for the sacral neuromodulation study was whether or not sacral neuromodulation might affect bladder filling by interfering with base-to-dome filling contractions (it does not).¹¹ What about smooth muscle relaxants? Do they interfere with normal bladder filling in animals or humans, or does the simultaneous decrease in bladder dome smooth muscle tone make any such effect negligible? It seems a reasonable question.

Finally, this innovation by Franken et al also allows for the utilization of continuous cystometry to achieve online, independent measurements of bladder volumes, urethral flow rates, post-void residual volumes etc, many of which are normally only achievable using single cystometrogram approaches.¹² This is very important if one is pursuing preclinical therapeutic research and utilizing cystometric methods and measurements. Bravo!